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Review

Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme (Review)

  • Authors:
    • Gang Wang
    • Jun-Jie Wang
    • Xing-Li Fu
    • Rui Guang
    • Shing-Shun Tony To
  • View Affiliations / Copyright

    Affiliations: Department of Hospital Pharmacy, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai 200235, P.R. China, Department of Health Technology and Informatics, Hong Kong Polytechnic University, Hung Hom, Kowloon Hong Kong, SAR, P.R. China
  • Pages: 657-670
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    Published online on: December 9, 2016
       https://doi.org/10.3892/or.2016.5309
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Abstract

Cell metabolism can be reprogrammed by tissue hypoxia leading to cell transformation and glioblastoma multiforme (GBM) progression. In response to hypoxia, GBM cells are able to express a transcription factor called hypoxia inducible factor-1 (HIF-1). HIF-1 belongs to a family of heterodimeric proteins that includes HIF-1α and HIF-1β subunits. HIF-1α has been reported to play a pivotal role in GBM development and progression. In the present review, we discuss the role of HIF-1α in glucose uptake, cancer proliferation, cell mobility and chemoresistance in GBM. Evidence from previous studies indicates that HIF-1α regulates angiogenesis, metabolic and transcriptional signaling pathways. Examples of such are the EGFR, PI3K/Akt and MAPK/ERK pathways. It affects cell migration and invasion by regulating glucose metabolism and growth in GBM cells. The present review focuses on the strategies through which to target HIF-1α and the related downstream genes highlighting their regulatory roles in angiogenesis, apoptosis, migration and glucose metabolism for the development of future GBM therapeutics. Combined treatment with inhibitors of HIF-1α and glycolysis may enhance antitumor effects in clinical settings.
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1 

Søndergaard KL, Hilton DA, Penney M, Ollerenshaw M and Demaine AG: Expression of hypoxia-inducible factor 1α in tumours of patients with glioblastoma. Neuropathol Appl Neurobiol. 28:210–217. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Solaini G, Baracca A, Lenaz G and Sgarbi G: Hypoxia and mitochondrial oxidative metabolism. Biochim Biophys Acta. 1797:1171–1177. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Wang GL, Jiang BH, Rue EA and Semenza GL: Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA. 92:5510–5514. 1995. View Article : Google Scholar : PubMed/NCBI

4 

Jewell UR, Kvietikova I, Scheid A, Bauer C, Wenger RH and Gassmann M: Induction of HIF-1alpha in response to hypoxia is instantaneous. FASEB J. 15:1312–1314. 2001.PubMed/NCBI

5 

Huang LE, Gu J, Schau M and Bunn HF: Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci USA. 95:7987–7992. 1998. View Article : Google Scholar : PubMed/NCBI

6 

Salceda S and Caro J: Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J Biol Chem. 272:22642–22647. 1997. View Article : Google Scholar : PubMed/NCBI

7 

Majmundar AJ, Wong WJ and Simon MC: Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 40:294–309. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Papandreou I, Cairns RA, Fontana L, Lim AL and Denko NC: HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 3:187–197. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Rankin EB and Giaccia AJ: The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ. 15:678–685. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Zundel W, Schindler C, Haas-Kogan D, Koong A, Kaper F, Chen E, Gottschalk AR, Ryan HE, Johnson RS, Jefferson AB, et al: Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev. 14:391–396. 2000.PubMed/NCBI

11 

Wang G, Wang J, Zhao H, Wang J and To SS Tony: The role of Myc and let-7a in glioblastoma, glucose metabolism and response to therapy. Arch Biochem Biophys. 580:84–92. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Li J, Zhu S, Tong J, Hao H, Yang J, Liu Z and Wang Y: Suppression of lactate dehydrogenase A compromises tumor progression by downregulation of the Warburg effect in glioblastoma. Neuroreport. 27:110–115. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Özcan E and Çakır T: Reconstructed metabolic network models predict flux-level metabolic reprogramming in glioblastoma. Front Neurosci. 10:1562016. View Article : Google Scholar : PubMed/NCBI

14 

Wu J, Liu Y, Cho K, Dong X, Teng L, Han D, Liu H, Chen X, Chen X, Hou X, et al: Downregulation of TRAP1 sensitizes glioblastoma cells to temozolomide chemotherapy through regulating metabolic reprogramming. Neuroreport. 27:136–144. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Yuen CA, Asuthkar S, Guda MR, Tsung AJ and Velpula KK: Cancer stem cell molecular reprogramming of the Warburg effect in glioblastomas: A new target gleaned from an old concept. CNS Oncol. 5:101–108. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Jiang W, Finniss S, Cazacu S, Xiang C, Brodie Z, Mikkelsen T, Poisson L, Shackelford DB and Brodie C: Repurposing phenformin for the targeting of glioma stem cells and the treatment of glioblastoma. Oncotarget. Jul 29–2016.(Epub ahead of print). doi: 10.18632/oncotarget.10919.

17 

Shen H, Hau E, Joshi S, Dilda PJ and McDonald KL: Sensitization of glioblastoma cells to irradiation by modulating the glucose metabolism. Mol Cancer Ther. 14:1794–1804. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Yang W, Wei J, Guo T, Shen Y and Liu F: Knockdown of miR-210 decreases hypoxic glioma stem cells stemness and radioresistance. Exp Cell Res. 326:22–35. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Agrawal R, Pandey P, Jha P, Dwivedi V, Sarkar C and Kulshreshtha R: Hypoxic signature of microRNAs in glioblastoma: Insights from small RNA deep sequencing. BMC Genomics. 15:6862014. View Article : Google Scholar : PubMed/NCBI

20 

Velpula KK, Bhasin A, Asuthkar S and Tsung AJ: Combined targeting of PDK1 and EGFR triggers regression of glioblastoma by reversing the Warburg effect. Cancer Res. 73:7277–7289. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Nie Q, Guo P, Guo L, Lan J, Lin Y, Guo F, Zhou S, Ge J, Mao Q, Li X, et al: Overexpression of isocitrate dehydrogenase-1R123H enhances the proliferation of A172 glioma cells via aerobic glycolysis. Mol Med Rep. 11:3715–3721. 2015.PubMed/NCBI

22 

Inukai M, Hara A, Yasui Y, Kumabe T, Matsumoto T and Saegusa M: Hypoxia-mediated cancer stem cells in pseudopalisades with activation of hypoxia-inducible factor-1α/Akt axis in glioblastoma. Hum Pathol. 46:1496–1505. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Xu G, Wang M, Xie W and Bai X: Hypoxia-inducible factor-1 alpha C1772T gene polymorphism and glioma risk: A hospital-based case-control study from China. Genet Test Mol Biomarkers. 15:461–464. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Adams DJ, Waud WR, Wani MC, Manikumar G, Flowers JL, Driscoll TA and Morgan LR: BACPTDP: A water-soluble camptothecin pro-drug with enhanced activity in hypoxic/acidic tumors. Cancer Chemother Pharmacol. 67:855–865. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Florczyk SJ, Wang K, Jana S, Wood DL, Sytsma SK, Sham JG, Kievit FM and Zhang M: Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM. Biomaterials. 34:10143–10150. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Maroni P, Matteucci E, Drago L, Banfi G, Bendinelli P and Desiderio MA: Hypoxia induced E-cadherin involving regulators of Hippo pathway due to HIF-1α stabilization/nuclear translocation in bone metastasis from breast carcinoma. Exp Cell Res. 330:287–299. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Lv L, Yuan J, Huang T, Zhang C, Zhu Z, Wang L, Jiang G and Zeng F: Stabilization of Snail by HIF-1α and TNF-α is required for hypoxia-induced invasion in prostate cancer PC3 cells. Mol Biol Rep. 41:4573–4582. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Mashiko R, Takano S, Ishikawa E, Yamamoto T, Nakai K and Matsumura A: Hypoxia-inducible factor 1α expression is a prognostic biomarker in patients with astrocytic tumors associated with necrosis on MR image. J Neurooncol. 102:43–50. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Birner P, Piribauer M, Fischer I, Gatterbauer B, Marosi C, Ambros PF, Ambros IM, Bredel M, Oberhuber G, Rössler K, et al: Vascular patterns in glioblastoma influence clinical outcome and associate with variable expression of angiogenic proteins: Evidence for distinct angiogenic subtypes. Brain Pathol. 13:133–143. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Flynn JR, Wang L, Gillespie DL, Stoddard GJ, Reid JK, Owens J, Ellsworth GB, Salzman KL, Kinney AY and Jensen RL: Hypoxia-regulated protein expression, patient characteristics, and preoperative imaging as predictors of survival in adults with glioblastoma multiforme. Cancer. 113:1032–1042. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Yuan G, Yan SF, Xue H, Zhang P, Sun JT and Li G: Cucurbitacin I induces protective autophagy in glioblastoma in vitro and in vivo. J Biol Chem. 289:10607–10619. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Yang YT, Ju TC and Yang DI: Induction of hypoxia inducible factor-1 attenuates metabolic insults induced by 3-nitropropionic acid in rat C6 glioma cells. J Neurochem. 93:513–525. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Qiang L, Wu T, Zhang HW, Lu N, Hu R, Wang YJ, Zhao L, Chen FH, Wang XT, You QD, et al: HIF-1α is critical for hypoxia-mediated maintenance of glioblastoma stem cells by activating Notch signaling pathway. Cell Death Differ. 19:284–294. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Gammoh N, Fraser J, Puente C, Syred HM, Kang H, Ozawa T, Lam D, Acosta JC, Finch AJ, Holland E, et al: Suppression of autophagy impedes glioblastoma development and induces senescence. Autophagy. 12:1431–1439. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Maugeri G, D'Amico A Grazia, Reitano R, Magro G, Cavallaro S, Salomone S and D'Agata V: PACAP and VIP inhibit the invasiveness of glioblastoma cells exposed to hypoxia through the regulation of HIFs and EGFR expression. Front Pharmacol. 7:1392016. View Article : Google Scholar : PubMed/NCBI

36 

Li J, Ke Y, Huang M, Huang S and Liang Y: Inhibitory effects of B-cell lymphoma 2 on the vasculogenic mimicry of hypoxic human glioma cells. Exp Ther Med. 9:977–981. 2015.PubMed/NCBI

37 

Lin H, Patel S, Affleck VS, Wilson I, Turnbull DM, Joshi AR, Maxwell R and Stoll EA: Fatty acid oxidation is required for the respiration and proliferation of malignant glioma cells. Neuro Oncol. Jun 29–2016.(Epub ahead of print). pii: now128.

38 

Han D, Wei W, Chen X, Zhang Y, Wang Y, Zhang J, Wang X, Yu T, Hu Q, Liu N, et al: NF-κB/RelA-PKM2 mediates inhibition of glycolysis by fenofibrate in glioblastoma cells. Oncotarget. 6:26119–26128. 2015. View Article : Google Scholar : PubMed/NCBI

39 

Womeldorff M, Gillespie D and Jensen RL: Hypoxia-inducible factor-1 and associated upstream and downstream proteins in the pathophysiology and management of glioblastoma. Neurosurg Focus. 37:E82014. View Article : Google Scholar : PubMed/NCBI

40 

Xie Q, Bao X, Chen ZH, Xu Y, Keep RF, Muraszko KM, Xi G and Hua Y: Role of protease-activated receptor-1 in glioma growth. Acta Neurochir. (Suppl 121). S355–S360. 2016.

41 

Ahmad F, Dixit D, Joshi SD and Sen E: G9a inhibition induced PKM2 regulates autophagic responses. Int J Biochem Cell Biol. 78:87–95. 2016. View Article : Google Scholar : PubMed/NCBI

42 

Okamoto K, Ito D, Miyazaki K, Watanabe S, Tohyama O, Yokoi A, Ozawa Y, Asano M, Kawamura T, Yamane Y, et al: Microregional antitumor activity of a small-molecule hypoxia-inducible factor 1 inhibitor. Int J Mol Med. 29:541–549. 2012.PubMed/NCBI

43 

Wei J, Wu A, Kong LY, Wang Y, Fuller G, Fokt I, Melillo G, Priebe W and Heimberger AB: Hypoxia potentiates glioma-mediated immunosuppression. PLoS One. 6:e161952011. View Article : Google Scholar : PubMed/NCBI

44 

Kucharzewska P, Christianson HC, Welch JE, Svensson KJ, Fredlund E, Ringnér M, Mörgelin M, Bourseau-Guilmain E, Bengzon J and Belting M: Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proc Natl Acad Sci USA. 110:7312–7317. 2013. View Article : Google Scholar : PubMed/NCBI

45 

Pore N, Jiang Z, Shu HK, Bernhard E, Kao GD and Maity A: Akt1 activation can augment hypoxia-inducible factor-1alpha expression by increasing protein translation through a mammalian target of rapamycin-independent pathway. Mol Cancer Res. 4:471–479. 2006. View Article : Google Scholar : PubMed/NCBI

46 

Joshi S, Singh AR and Durden DL: MDM2 regulates hypoxic hypoxia-inducible factor 1α stability in an E3 ligase, proteasome, and PTEN-phosphatidylinositol 3-kinase-AKT-dependent manner. J Biol Chem. 289:22785–22797. 2014. View Article : Google Scholar : PubMed/NCBI

47 

Muh CR, Joshi S, Singh AR, Kesari S, Durden DL and Makale MT: PTEN status mediates 2ME2 anti-tumor efficacy in preclinical glioblastoma models: Role of HIF1α suppression. J Neurooncol. 116:89–97. 2014. View Article : Google Scholar : PubMed/NCBI

48 

Hsu CC, Wang CH, Wu LC, Hsia CY, Chi CW, Yin PH, Chang CJ, Sung MT, Wei YH, Lu SH, et al: Mitochondrial dysfunction represses HIF-1α protein synthesis through AMPK activation in human hepatoma HepG2 cells. Biochim Biophys Acta. 1830:4743–4751. 2013. View Article : Google Scholar : PubMed/NCBI

49 

Chae YC, Vaira V, Caino MC, Tang HY, Seo JH, Kossenkov AV, Ottobrini L, Martelli C, Lucignani G, Bertolini I, et al: Mitochondrial Akt regulation of hypoxic tumor reprogramming. Cancer Cell. 30:257–272. 2016. View Article : Google Scholar : PubMed/NCBI

50 

Razorenova OV, Castellini L, Colavitti R, Edgington LE, Nicolau M, Huang X, Bedogni B, Mills EM, Bogyo M and Giaccia AJ: The apoptosis repressor with a CARD domain (ARC) gene is a direct hypoxia-inducible factor 1 target gene and promotes survival and proliferation of VHL-deficient renal cancer cells. Mol Cell Biol. 34:739–751. 2014. View Article : Google Scholar : PubMed/NCBI

51 

Lo Dico A, Martelli C, Valtorta S, Raccagni I, Diceglie C, Belloli S, Gianelli U, Vaira V, Politi LS, Bosari S, et al: Identification of imaging biomarkers for the assessment of tumour response to different treatments in a preclinical glioma model. Eur J Nucl Med Mol Imaging. 42:1093–1105. 2015. View Article : Google Scholar : PubMed/NCBI

52 

Madan E, Dikshit B, Gowda SH, Srivastava C, Sarkar C, Chattopadhyay P, Sinha S and Chosdol K: FAT1 is a novel upstream regulator of HIF1α and invasion of high grade glioma. Int J Cancer. 139:2570–2582. 2016. View Article : Google Scholar : PubMed/NCBI

53 

Minchenko OH, Kharkova AP, Minchenko DO and Karbovskyi LL: Effect of hypoxia on the expression of genes that encode some IGFBP and CCN proteins in U87 glioma cells depends on IRE1 signaling. Ukr Biochem J. 87:52–63. 2015. View Article : Google Scholar : PubMed/NCBI

54 

Hu J and Wang XF: HIF-miR-215-KDM1B promotes glioma-initiating cell adaptation to hypoxia. Cell Cycle. 15:1939–1940. 2016. View Article : Google Scholar : PubMed/NCBI

55 

Hu J, Sun T, Wang H, Chen Z, Wang S, Yuan L, Liu T, Li HR, Wang P, Feng Y, et al: MiR-215 is induced post-transcriptionally via HIF-Drosha complex and mediates glioma-initiating cell adaptation to hypoxia by targeting KDM1B. Cancer Cell. 29:49–60. 2016. View Article : Google Scholar : PubMed/NCBI

56 

Lan J, Xue Y, Chen H, Zhao S, Wu Z, Fang J, Han C and Lou M: Hypoxia-induced miR-497 decreases glioma cell sensitivity to TMZ by inhibiting apoptosis. FEBS Lett. 588:3333–3339. 2014. View Article : Google Scholar : PubMed/NCBI

57 

Xue H, Guo X, Han X, Yan S, Zhang J, Xu S, Li T, Guo X, Zhang P, Gao X, et al: MicroRNA-584-3p, a novel tumor suppressor and prognostic marker, reduces the migration and invasion of human glioma cells by targeting hypoxia-induced ROCK1. Oncotarget. 7:4785–4805. 2016.PubMed/NCBI

58 

Jensen RL: Brain tumor hypoxia: Tumorigenesis, angiogenesis, imaging, pseudoprogression, and as a therapeutic target. J Neurooncol. 92:317–335. 2009. View Article : Google Scholar : PubMed/NCBI

59 

Tivnan A and McDonald KL: Current progress for the use of miRNAs in glioblastoma treatment. Mol Neurobiol. 48:757–768. 2013. View Article : Google Scholar : PubMed/NCBI

60 

Kalkan R: Hypoxia is the driving force behind GBM and could be a new tool in GBM treatment. Crit Rev Eukaryot Gene Expr. 25:363–369. 2015. View Article : Google Scholar : PubMed/NCBI

61 

Harris AL: Hypoxia - a key regulatory factor in tumour growth. Nat Rev Cancer. 2:38–47. 2002. View Article : Google Scholar : PubMed/NCBI

62 

Höckel M and Vaupel P: Tumor hypoxia: Definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst. 93:266–276. 2001. View Article : Google Scholar : PubMed/NCBI

63 

Ruan K, Song G and Ouyang G: Role of hypoxia in the hallmarks of human cancer. J Cell Biochem. 107:1053–1062. 2009. View Article : Google Scholar : PubMed/NCBI

64 

Oliver L, Olivier C, Marhuenda FB, Campone M and Vallette FM: Hypoxia and the malignant glioma microenvironment: Regulation and implications for therapy. Curr Mol Pharmacol. 2:263–284. 2009. View Article : Google Scholar : PubMed/NCBI

65 

Tang JH, Ma ZX, Huang GH, Xu QF, Xiang Y, Li N, Sidlauskas K, Zhang EE and Lv SQ: Downregulation of HIF-1a sensitizes U251 glioma cells to the temozolomide (TMZ) treatment. Exp Cell Res. 343:148–158. 2016. View Article : Google Scholar : PubMed/NCBI

66 

Chen W, Xiao Z, Zhao Y, Huang L and Du G: HIF-1α inhibition sensitizes pituitary adenoma cells to temozolomide by regulating MGMT expression. Oncol Rep. 30:2495–2501. 2013.PubMed/NCBI

67 

Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, Xu L, Hicklin DJ, Fukumura D, di Tomaso E, et al: Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: Role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell. 6:553–563. 2004. View Article : Google Scholar : PubMed/NCBI

68 

Wick A, Wick W, Waltenberger J, Weller M, Dichgans J and Schulz JB: Hypoxic neuroprotection requires sequential activation of vascular endothelial growth factor receptor and Akt. J Neurosci. 22:6401–6407. 2002.PubMed/NCBI

69 

Henze AT, Riedel J, Diem T, Wenner J, Flamme I, Pouyseggur J, Plate KH and Acker T: Prolyl hydroxylases 2 and 3 act in gliomas as protective negative feedback regulators of hypoxia-inducible factors. Cancer Res. 70:357–366. 2010. View Article : Google Scholar : PubMed/NCBI

70 

Mancini M, Gariboldi MB, Taiana E, Bonzi MC, Craparotta I, Pagin M and Monti E: Co-targeting the IGF system and HIF-1 inhibits migration and invasion by (triple-negative) breast cancer cells. Br J Cancer. 110:2865–2873. 2014. View Article : Google Scholar : PubMed/NCBI

71 

Onnis B, Rapisarda A and Melillo G: Development of HIF-1 inhibitors for cancer therapy. J Cell Mol Med. 13:2780–2786. 2009. View Article : Google Scholar : PubMed/NCBI

72 

Xia Y, Choi HK and Lee K: Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors. Eur J Med Chem. 49:24–40. 2012. View Article : Google Scholar : PubMed/NCBI

73 

Huang SW, Kao JK, Wu CY, Wang ST, Lee HC, Liang SM, Chen YJ and Shieh JJ: Targeting aerobic glycolysis and HIF-1alpha expression enhance imiquimod-induced apoptosis in cancer cells. Oncotarget. 5:1363–1381. 2014. View Article : Google Scholar : PubMed/NCBI

74 

Dai P, Akimaru H, Tanaka Y, Maekawa T, Nakafuku M and Ishii S: Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by GLI3. J Biol Chem. 274:8143–8152. 1999. View Article : Google Scholar : PubMed/NCBI

75 

Regl G, Neill GW, Eichberger T, Kasper M, Ikram MS, Koller J, Hintner H, Quinn AG, Frischauf AM and Aberger F: Human GLI2 and GLI1 are part of a positive feedback mechanism in Basal Cell Carcinoma. Oncogene. 21:5529–5539. 2002. View Article : Google Scholar : PubMed/NCBI

76 

Fedorchuk AG, Pyaskovskaya ON, Gorbik GV, Prokhorova IV, Kolesnik DL and Solyanik GI: Effectiveness of sodium dichloroacetate against glioma C6 depends on administration schedule and dosage. Exp Oncol. 38:80–83. 2016.PubMed/NCBI

77 

Wang H, Feng H and Zhang Y: Resveratrol inhibits hypoxia-induced glioma cell migration and invasion by the p-STAT3/miR-34a axis. Neoplasma. 63:532–539. 2016. View Article : Google Scholar : PubMed/NCBI

78 

Li S, Wang J, Wei Y, Liu Y, Ding X, Dong B, Xu Y and Wang Y: Crucial role of TRPC6 in maintaining the stability of HIF-1α in glioma cells under hypoxia. J Cell Sci. 128:3317–3329. 2015. View Article : Google Scholar : PubMed/NCBI

79 

Luan W, Wang Y, Chen X, Shi Y, Wang J, Zhang J, Qian J, Li R, Tao T, Wei W, et al: PKM2 promotes glucose metabolism and cell growth in gliomas through a mechanism involving a let-7a/c-Myc/hnRNPA1 feedback loop. Oncotarget. 6:13006–13018. 2015. View Article : Google Scholar : PubMed/NCBI

80 

Wan YY, Zhang JF, Yang ZJ, Jiang LP, Wei YF, Lai QN, Wang JB, Xin HB and Han XJ: Involvement of Drp1 in hypoxia-induced migration of human glioblastoma U251 cells. Oncol. 32:619–626. 2014.

81 

Adamski J, Price A, Dive C and Makin G: Hypoxia-induced cytotoxic drug resistance in osteosarcoma is independent of HIF-1Alpha. PLoS One. 8:e653042013. View Article : Google Scholar : PubMed/NCBI

82 

Cook KM, Hilton ST, Mecinovic J, Motherwell WB, Figg WD and Schofield CJ: Epidithiodiketopiperazines block the interaction between hypoxia-inducible factor-1alpha (HIF-1alpha) and p300 by a zinc ejection mechanism. J Biol Chem. 284:26831–26838. 2009. View Article : Google Scholar : PubMed/NCBI

83 

Maples KR, Green AR and Floyd RA: Nitrone-related therapeutics: Potential of NXY-059 for the treatment of acute ischaemic stroke. CNS Drugs. 18:1071–1084. 2004. View Article : Google Scholar : PubMed/NCBI

84 

Gillespie DL, Whang K, Ragel BT, Flynn JR, Kelly DA and Jensen RL: Silencing of hypoxia inducible factor-1alpha by RNA interference attenuates human glioma cell growth in vivo. Clin Cancer Res. 13:2441–2448. 2007. View Article : Google Scholar : PubMed/NCBI

85 

Sydserff SG, Borelli AR, Green AR and Cross AJ: Effect of NXY-059 on infarct volume after transient or permanent middle cerebral artery occlusion in the rat; studies on dose, plasma concentration and therapeutic time window. Br J Pharmacol. 135:103–112. 2002. View Article : Google Scholar : PubMed/NCBI

86 

Hashizume R, Ozawa T, Dinca EB, Banerjee A, Prados MD, James CD and Gupta N: A human brainstem glioma xenograft model enabled for bioluminescence imaging. J Neurooncol. 96:151–159. 2010. View Article : Google Scholar : PubMed/NCBI

87 

de Souza PC, Smith N, Pody R, He T, Njoku C, Silasi-Mansat R, Lupu F, Meek B, Chen H, Dong Y, et al: OKN-007 decreases VEGFR-2 levels in a preclinical GL261 mouse glioma model. Am J Nucl Med Mol Imaging. 5:363–378. 2015.PubMed/NCBI

88 

Bourne DW: BOOMER, a simulation and modeling program for pharmacokinetic and pharmacodynamic data analysis. Comput Methods Programs Biomed. 29:191–195. 1989. View Article : Google Scholar : PubMed/NCBI

89 

Yamaoka K, Nakagawa T and Uno T: Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm. 6:165–175. 1978. View Article : Google Scholar : PubMed/NCBI

90 

de Souza P Coutinho, Mallory S, Smith N, Saunders D, Li XN, McNall-Knapp RY, Fung KM and Towner RA: Inhibition of pediatric glioblastoma tumor growth by the anti-cancer agent OKN-007 in orthotopic mouse xenografts. PLoS One. 10:e01342762015. View Article : Google Scholar : PubMed/NCBI

91 

Liu D, Cao G, Cen Y, Liu T, Peng W, Sun J, Li X and Zhou H: The radiosensitizing effect of CpG ODN107 on human glioma cells is tightly related to its antiangiogenic activity via suppression of HIF-1α/VEGF pathway. Int Immunopharmacol. 17:237–244. 2013. View Article : Google Scholar : PubMed/NCBI

92 

Wellmann S, Bettkober M, Zelmer A, Seeger K, Faigle M, Eltzschig HK and Bührer C: Hypoxia upregulates the histone demethylase JMJD1A via HIF-1. Biochem Biophys Res Commun. 372:892–897. 2008. View Article : Google Scholar : PubMed/NCBI

93 

Belozerov VE and Van Meir EG: Hypoxia inducible factor-1: A novel target for cancer therapy. Anticancer Drugs. 16:901–909. 2005. View Article : Google Scholar : PubMed/NCBI

94 

Melillo G: Inhibiting hypoxia-inducible factor 1 for cancer therapy. Mol Cancer Res. 4:601–605. 2006. View Article : Google Scholar : PubMed/NCBI

95 

Semenza GL: Evaluation of HIF-1 inhibitors as anticancer agents. Drug Discov Today. 12:853–859. 2007. View Article : Google Scholar : PubMed/NCBI

96 

Lee P, Murphy B, Miller R, Menon V, Banik NL, Giglio P, Lindhorst SM, Varma AK, Vandergrift WA III, Patel SJ, et al: Mechanisms and clinical significance of histone deacetylase inhibitors: Epigenetic glioblastoma therapy. Anticancer Res. 35:615–625. 2015.PubMed/NCBI

97 

Qian DZ, Wang X, Kachhap SK, Kato Y, Wei Y, Zhang L, Atadja P and Pili R: The histone deacetylase inhibitor NVP-LAQ824 inhibits angiogenesis and has a greater antitumor effect in combination with the vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584. Cancer Res. 64:6626–6634. 2004. View Article : Google Scholar : PubMed/NCBI

98 

Kerbel RS: Tumor angiogenesis. N Engl J Med. 358:2039–2049. 2008. View Article : Google Scholar : PubMed/NCBI

99 

Moeini A, Cornellà H and Villanueva A: Emerging signaling pathways in hepatocellular carcinoma. Liver Cancer. 1:83–93. 2012. View Article : Google Scholar : PubMed/NCBI

100 

von Burstin J, Eser S, Paul MC, Seidler B, Brandl M, Messer M, von Werder A, Schmidt A, Mages J, Pagel P, et al: E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex. Gastroenterology. 137:361–371, 371.e1–371.e5. 2009. View Article : Google Scholar : PubMed/NCBI

101 

Falkenberg KJ and Johnstone RW: Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov. 13:673–691. 2014. View Article : Google Scholar : PubMed/NCBI

102 

Singh MM, Johnson B, Venkatarayan A, Flores ER, Zhang J, Su X, Barton M, Lang F and Chandra J: Preclinical activity of combined HDAC and KDM1A inhibition in glioblastoma. Neuro Oncol. 17:1463–1473. 2015. View Article : Google Scholar : PubMed/NCBI

103 

Scroggins BT, Robzyk K, Wang D, Marcu MG, Tsutsumi S, Beebe K, Cotter RJ, Felts S, Toft D and Karnitz L: An acetylation site in the middle domain of Hsp90 regulates chaperone function. Mol Cell. 25:151–159. 2007. View Article : Google Scholar : PubMed/NCBI

104 

Siegel D, Hussein M, Belani C, Robert F, Galanis E, Richon VM, Garcia-Vargas J, Sanz-Rodriguez C and Rizvi S: Vorinostat in solid and hematologic malignancies. J Hematol Oncol. 2:312009. View Article : Google Scholar : PubMed/NCBI

105 

Miyar A, Habibi I, Ebrahimi A, Mansourpour D, Mokarizadeh A, Rajabi A, Farshgar R, Eshaghzadeh M, Zamani-Ahmadmahmudi M and Nodushan SM: Predictive and prognostic value of TLR9 and NFKBIA gene expression as potential biomarkers for human glioma diagnosis. J Neurol Sci. 368:314–317. 2016. View Article : Google Scholar : PubMed/NCBI

106 

Zagzag D, Nomura M, Friedlander DR, Blanco CY, Gagner JP, Nomura N and Newcomb EW: Geldanamycin inhibits migration of glioma cells in vitro: A potential role for hypoxia-inducible factor (HIF-1alpha) in glioma cell invasion. J Cell Physiol. 196:394–402. 2003. View Article : Google Scholar : PubMed/NCBI

107 

Simioni C, Cani A, Martelli AM, Zauli G, Alameen AA, Ultimo S, Tabellini G, McCubrey JA, Capitani S and Neri LM: The novel dual PI3K/mTOR inhibitor NVP-BGT226 displays cytotoxic activity in both normoxic and hypoxic hepatocarcinoma cells. Oncotarget. 6:17147–17160. 2015. View Article : Google Scholar : PubMed/NCBI

108 

Huang WJ, Liang YC, Chuang SE, Chi LL, Lee CY, Lin CW, Chen AL, Huang JS, Chiu CJ, Lee CF, Huang CY and Chen CN: NBM-HD-1: A novel histone deacetylase inhibitor with anticancer activity. Evid Based Complement Alternat Med. 2012:7814172012. View Article : Google Scholar : PubMed/NCBI

109 

Huang WJ, Lin CW, Lee CY, Chi LL, Chao YC, Wang HN, Chiou BL, Chen TJ, Huang CY and Chen CN: NBM-HD-3, a novel histone deacetylase inhibitor with anticancer activity through modulation of PTEN and AKT in brain cancer cells. J Ethnopharmacol. 136:156–167. 2011. View Article : Google Scholar : PubMed/NCBI

110 

Zhang W, Lv S, Liu J, Zang Z, Yin J, An N, Yang H and Song Y: PCI-24781 down-regulates EZH2 expression and then promotes glioma apoptosis by suppressing the PIK3K/Akt/mTOR pathway. Genet Mol Biol. 37:716–724. 2014. View Article : Google Scholar : PubMed/NCBI

111 

Redjal N, Reinshagen C, Le A, Walcott BP, McDonnell E, Dietrich J and Nahed BV: Valproic acid, compared to other antiepileptic drugs, is associated with improved overall and progression-free survival in glioblastoma but worse outcome in grade II/III gliomas treated with temozolomide. J Neurooncol. 127:505–514. 2016. View Article : Google Scholar : PubMed/NCBI

112 

Hoja S, Schulze M, Rehli M, Proescholdt M, Herold-Mende C, Hau P and Riemenschneider MJ: Molecular dissection of the valproic acid effects on glioma cells. Oncotarget. Aug 18–2016.(Epub ahead of print). doi: 10.18632/oncotarget.11379. View Article : Google Scholar : PubMed/NCBI

113 

Pont LM Berghauser, Kleijn A, Kloezeman JJ, van den Bossche W, Kaufmann JK, de Vrij J, Leenstra S, Dirven CM and Lamfers ML: The HDAC inhibitors scriptaid and LBH589 combined with the oncolytic virus Delta24-RGD exert enhanced anti-tumor efficacy in patient-derived glioblastoma cells. PLoS One. 10:e01270582015. View Article : Google Scholar : PubMed/NCBI

114 

Vasilatos SN, Katz TA, Oesterreich S, Wan Y, Davidson NE and Huang Y: Crosstalk between lysine-specific demethylase 1 (LSD1) and histone deacetylases mediates antineoplastic efficacy of HDAC inhibitors in human breast cancer cells. Carcinogenesis. 34:1196–1207. 2013. View Article : Google Scholar : PubMed/NCBI

115 

Wang Z, Wang N, Han S, Wang D, Mo S, Yu L, Huang H, Tsui K, Shen J and Chen J: Dietary compound isoliquiritigenin inhibits breast cancer neoangiogenesis via VEGF/VEGFR-2 signaling pathway. PLoS One. 8:e685662013. View Article : Google Scholar : PubMed/NCBI

116 

Zhao S, Chang H, Ma P, Gao G, Jin C, Zhao X, Zhou W and Jin B: Inhibitory effect of DNA topoisomerase inhibitor isoliquiritigenin on the growth of glioma cells. Int J Clin Exp Pathol. 8:12577–12582. 2015.PubMed/NCBI

117 

Zhou GS, Song LJ and Yang B: Isoliquiritigenin inhibits proliferation and induces apoptosis of U87 human glioma cells in vitro. Mol Med Rep. 7:531–536. 2013.PubMed/NCBI

118 

Ma J, Han LZ, Liang H, Mi C, Shi H, Lee JJ and Jin X: Celastrol inhibits the HIF-1α pathway by inhibition of mTOR/p70S6K/eIF4E and ERK1/2 phosphorylation in human hepatoma cells. Oncol Rep. 32:235–242. 2014.PubMed/NCBI

119 

Zhou YX and Huang YL: Antiangiogenic effect of celastrol on the growth of human glioma: An in vitro and in vivo study. Chin Med J. 122:1666–1673. 2009.PubMed/NCBI

120 

Huang Y, Zhou Y, Fan Y and Zhou D: Celastrol inhibits the growth of human glioma xenografts in nude mice through suppressing VEGFR expression. Cancer Lett. 264:101–106. 2008. View Article : Google Scholar : PubMed/NCBI

121 

Bordji K, Grandval A, Cuhna-Alves L, Lechapt-Zalcman E and Bernaudin M: Hypoxia-inducible factor-2α (HIF-2α), but not HIF-1α, is essential for hypoxic induction of class III β-tubulin expression in human glioblastoma cells. FEBS J. 281:5220–5236. 2014. View Article : Google Scholar : PubMed/NCBI

122 

Bache M, Rot S, Keßler J, Güttler A, Wichmann H, Greither T, Wach S, Taubert H, Söling A, Bilkenroth U, et al: mRNA expression levels of hypoxia-induced and stem cell-associated genes in human glioblastoma. Oncol Rep. 33:3155–3161. 2015.PubMed/NCBI

123 

Jonasch E, Futreal PA, Davis IJ, Bailey ST, Kim WY, Brugarolas J, Giaccia AJ, Kurban G, Pause A, Frydman J, et al: State of the science: An update on renal cell carcinoma. Mol Cancer Res. 10:859–880. 2012. View Article : Google Scholar : PubMed/NCBI

124 

Bhagat M, Palanichamy JK, Ramalingam P, Mudassir M, Irshad K, Chosdol K, Sarkar C, Seth P, Goswami S, Sinha S, et al: HIF-2α mediates a marked increase in migration and stemness characteristics in a subset of glioma cells under hypoxia by activating an Oct-4/Sox-2-Mena (INV) axis. Int J Biochem Cell Biol. 74:60–71. 2016. View Article : Google Scholar : PubMed/NCBI

125 

Miranda-Gonçalves V, Granja S, Martinho O, Honavar M, Pojo M, Costa BM, Pires MM, Pinheiro C, Cordeiro M, Bebiano G, et al: Hypoxia-mediated upregulation of MCT1 expression supports the glycolytic phenotype of glioblastomas. Oncotarget. Jun 16–2016.(Epub ahead of print). doi: 10.18632/oncotarget.

126 

Zhang J, Zhu L, Fang J, Ge Z and Li X: LRG1 modulates epithelial-mesenchymal transition and angiogenesis in colorectal cancer via HIF-1α activation. J Exp Clin Cancer Res. 35:292016. View Article : Google Scholar : PubMed/NCBI

127 

Li S, Zhang J, Yang H, Wu C, Dang X and Liu Y: Copper depletion inhibits CoCl2-induced aggressive phenotype of MCF-7 cells via downregulation of HIF-1 and inhibition of Snail/Twist-mediated epithelial-mesenchymal transition. Sci Rep. 5:124102015. View Article : Google Scholar : PubMed/NCBI

128 

Ishii A, Kimura T, Sadahiro H, Kawano H, Takubo K, Suzuki M and Ikeda E: Histological characterization of the tumorigenic ‘peri-necrotic niche’ harboring quiescent stem-like tumor cells in glioblastoma. PLoS One. 11:e01473662016. View Article : Google Scholar : PubMed/NCBI

129 

Xu H, Rahimpour S, Nesvick CL, Zhang X, Ma J, Zhang M, Zhang G, Wang L, Yang C, Hong CS, et al: Activation of hypoxia signaling induces phenotypic transformation of glioma cells: Implications for bevacizumab antiangiogenic therapy. Oncotarget. 6:11882–11893. 2015. View Article : Google Scholar : PubMed/NCBI

130 

Clarke RH, Moosa S, Anzivino M, Wang Y, Floyd DH, Purow BW and Lee KS: Sustained radiosensitization of hypoxic glioma cells after oxygen pretreatment in an animal model of glioblastoma and in vitro models of tumor hypoxia. PLoS One. 9:e1111992014. View Article : Google Scholar : PubMed/NCBI

131 

Balamurugan K, Wang JM, Tsai HH, Sharan S, Anver M, Leighty R and Sterneck E: The tumour suppressor C/EBPδ inhibits FBXW7 expression and promotes mammary tumour metastasis. EMBO J. 29:4106–4117. 2010. View Article : Google Scholar : PubMed/NCBI

132 

Sudhagar S, Sathya S and Lakshmi BS: Rapid non-genomic signalling by 17β-oestradiol through c-Src involves mTOR-dependent expression of HIF-1α in breast cancer cells. Br J Cancer. 105:953–960. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang G, Wang J, Fu X, Guang R and To ST: Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme (Review). Oncol Rep 37: 657-670, 2017.
APA
Wang, G., Wang, J., Fu, X., Guang, R., & To, S.T. (2017). Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme (Review). Oncology Reports, 37, 657-670. https://doi.org/10.3892/or.2016.5309
MLA
Wang, G., Wang, J., Fu, X., Guang, R., To, S. T."Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme (Review)". Oncology Reports 37.2 (2017): 657-670.
Chicago
Wang, G., Wang, J., Fu, X., Guang, R., To, S. T."Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme (Review)". Oncology Reports 37, no. 2 (2017): 657-670. https://doi.org/10.3892/or.2016.5309
Copy and paste a formatted citation
x
Spandidos Publications style
Wang G, Wang J, Fu X, Guang R and To ST: Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme (Review). Oncol Rep 37: 657-670, 2017.
APA
Wang, G., Wang, J., Fu, X., Guang, R., & To, S.T. (2017). Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme (Review). Oncology Reports, 37, 657-670. https://doi.org/10.3892/or.2016.5309
MLA
Wang, G., Wang, J., Fu, X., Guang, R., To, S. T."Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme (Review)". Oncology Reports 37.2 (2017): 657-670.
Chicago
Wang, G., Wang, J., Fu, X., Guang, R., To, S. T."Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme (Review)". Oncology Reports 37, no. 2 (2017): 657-670. https://doi.org/10.3892/or.2016.5309
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