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Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth

  • Authors:
    • Yuan Liu
    • Tracy Murray-Stewart
    • Robert A. Casero
    • Ioannis Kagiampakis
    • Lihua Jin
    • Jiawen Zhang
    • Huihui Wang
    • Qi Che
    • Huan Tong
    • Jieqi Ke
    • Feizhou Jiang
    • Fangyuan Wang
    • Xiaoping Wan
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA, Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA, Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Shanghai Tongji University, Shanghai, P.R. China, Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, P.R. China, Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2011-2023
    |
    Published online on: May 2, 2017
       https://doi.org/10.3892/ijo.2017.3979
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Abstract

In order to improve the sensitivity of cervical cancer cells to irradiation therapy, we targeted hexokinase 2 (HK2), the first rate-limiting enzyme of glycolysis, and explore its role in cervical cancer cells. We suppressed HK2 expression and/or function by shRNA and/or metformin and found HK2 inhibition enhanced cells apoptosis with accelerating expression of cleaved PARP and caspase-3. HK2 inhibition also induced much inferior proliferation of cervical cancer cells both in vitro and in vivo with diminishing expression of mTOR, MIB and MGMT. Moreover, HK2 inhibition altered the metabolic profile of cervical cancer cells to one less dependent on glycolysis with a reinforcement of mitochondrial function and an ablation of lactification ability. Importantly, cervical cancer cells contained HK2 inhibition displayed more sensitivity to irradiation. Further results indicated that HPV16 E7 oncoprotein altered the glucose homeostasis of cervical cancer cells into glycolysis by coordinately promoting HK2 expression and its downregulation of glycolysis. Taken together, our findings supported a mechanism whereby targeting HK2 inhibition contributed to suppress HPV16 E7-induced tumor glycolysis metabolism phenotype, inhibiting tumor growth, and induced apoptosis, blocking the cancer cell energy sources and ultimately enhanced the sensitivity of HPV(+) cervical cancer cells to irradiation therapy.
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View References

1 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Kroemer G and Pouyssegur J: Tumor cell metabolism: Cancer's Achilles' heel. Cancer Cell. 13:472–482. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Hsu PP and Sabatini DM: Cancer cell metabolism: Warburg and beyond. Cell. 134:703–707. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Mathupala SP, Ko YH and Pedersen PL: Hexokinase II: Cancer's double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene. 25:4777–4786. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Mathupala SP, Rempel A and Pedersen PL: Glucose catabolism in cancer cells: Identification and characterization of a marked activation response of the type II hexokinase gene to hypoxic conditions. J Biol Chem. 276:43407–43412. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Wang W, Liu Z, Zhao L, Sun J, He Q, Yan W, Lu Z and Wang A: Hexokinase 2 enhances the metastatic potential of tongue squamous cell carcinoma via the SOD2–H2O2 pathway. Oncotarget. 8:3344–3354. 2017.

7 

Patra KC, Wang Q, Bhaskar PT, Miller L, Wang Z, Wheaton W, Chandel N, Laakso M, Muller WJ, Allen EL, et al: Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer. Cancer Cell. 24:213–228. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Wolf A, Agnihotri S, Micallef J, Mukherjee J, Sabha N, Cairns R, Hawkins C and Guha A: Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. J Exp Med. 208:313–326. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Bustamante E and Pedersen PL: High aerobic glycolysis of rat hepatoma cells in culture: Role of mitochondrial hexokinase. Proc Natl Acad Sci USA. 74:3735–3739. 1977. View Article : Google Scholar : PubMed/NCBI

10 

Kim JW and Dang CV: Multifaceted roles of glycolytic enzymes. Trends Biochem Sci. 30:142–150. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Mathupala SP, Ko YH and Pedersen PL: Hexokinase-2 bound to mitochondria: Cancer's stygian link to the 'Warburg Effect' and a pivotal target for effective therapy. Semin Cancer Biol. 19:17–24. 2009. View Article : Google Scholar

12 

Pastorino JG, Shulga N and Hoek JB: Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J Biol Chem. 277:7610–7618. 2002. View Article : Google Scholar

13 

Majewski N, Nogueira V, Bhaskar P, Coy PE, Skeen JE, Gottlob K, Chandel NS, Thompson CB, Robey RB and Hay N: Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol Cell. 16:819–830. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Gottlob K, Majewski N, Kennedy S, Kandel E, Robey RB and Hay N: Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev. 15:1406–1418. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Rockwell S, Dobrucki IT, Kim EY, Marrison ST and Vu VT: Hypoxia and radiation therapy: Past history, ongoing research, and future promise. Curr Mol Med. 9:442–458. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Shimura T, Kakuda S, Ochiai Y, Nakagawa H, Kuwahara Y, Takai Y, Kobayashi J, Komatsu K and Fukumoto M: Acquired radioresistance of human tumor cells by DNA-PK/AKT/GSK3beta-mediated cyclin D1 overexpression. Oncogene. 29:4826–4837. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Bolderson E, Richard DJ, Zhou BB and Khanna KK: Recent advances in cancer therapy targeting proteins involved in DNA double-strand break repair. Clin Cancer Res. 15:6314–6320. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Lehmann BD, McCubrey JA, Jefferson HS, Paine MS, Chappell WH and Terrian DM: A dominant role for p53-dependent cellular senescence in radiosensitization of human prostate cancer cells. Cell Cycle. 6:595–605. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Bergkvist GT, Argyle DJ, Pang LY, Muirhead R and Yool DA: Studies on the inhibition of feline EGFR in squamous cell carcinoma: Enhancement of radiosensitivity and rescue of resistance to small molecule inhibitors. Cancer Biol Ther. 11:927–937. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Baumann M, Krause M and Hill R: Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer. 8:545–554. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Brown JM and Giaccia AJ: The unique physiology of solid tumors: Opportunities (and problems) for cancer therapy. Cancer Res. 58:1408–1416. 1998.PubMed/NCBI

22 

Milosevic M, Warde P, Menard C, Chung P, Toi A, Ishkanian A, McLean M, Pintilie M, Sykes J, Gospodarowicz M, et al: Tumor hypoxia predicts biochemical failure following radiotherapy for clinically localized prostate cancer. Clin Cancer Res. 18:2108–2114. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Harada H: Hypoxia-inducible factor 1-mediated characteristic features of cancer cells for tumor radioresistance. J Radiat Res (Tokyo). 57(Suppl 1): i99–i105. 2016. View Article : Google Scholar

24 

Sattler UG and Mueller-Klieser W: The anti-oxidant capacity of tumour glycolysis. Int J Radiat Biol. 85:963–971. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Trachootham D, Alexandre J and Huang P: Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic approach? Nat Rev Drug Discov. 8:579–591. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Bui T and Thompson CB: Cancer's sweet tooth. Cancer Cell. 9:419–420. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Nakashima RA, Paggi MG and Pedersen PL: Contributions of glycolysis and oxidative phosphorylation to adenosine 5′-triphosphate production in AS-30D hepatoma cells. Cancer Res. 44:5702–5706. 1984.PubMed/NCBI

28 

Meng MB, Wang HH, Guo WH, Wu ZQ, Zeng XL, Zaorsky NG, Shi HS, Qian D, Niu ZM, Jiang B, et al: Targeting pyruvate kinase M2 contributes to radiosensitivity of non-small cell lung cancer cells in vitro and in vivo. Cancer Lett. 356B:985–993. 2015. View Article : Google Scholar

29 

Bol V, Bol A, Bouzin C, Labar D, Lee JA, Janssens G, Porporato PE, Sonveaux P, Feron O and Grégoire V: Reprogramming of tumor metabolism by targeting mitochondria improves tumor response to irradiation. Acta Oncol. 54:266–274. 2015. View Article : Google Scholar

30 

Pena-Rico MA, Calvo-Vidal MN, Villalonga-Planells R, Martínez-Soler F, Giménez-Bonafé P, Navarro-Sabaté À, Tortosa A, Bartrons R and Manzano A: TP53 induced glycolysis and apoptosis regulator (TIGAR) knockdown results in radio-sensitization of glioma cells. Radiother Oncol. 101:132–139. 2011. View Article : Google Scholar

31 

BelAiba RS, Djordjevic T, Bonello S, Flügel D, Hess J, Kietzmann T and Görlach A: Redox-sensitive regulation of the HIF pathway under non-hypoxic conditions in pulmonary artery smooth muscle cells. Biol Chem. 385:249–257. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM and Schumacker PT: Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: A mechanism of O2 sensing. J Biol Chem. 275:25130–25138. 2000. View Article : Google Scholar : PubMed/NCBI

33 

Cheng Y, Chen G, Hong L, Zhou L, Hu M, Li B, Huang J, Xia L and Li C: How does hypoxia inducible factor-1α participate in enhancing the glycolysis activity in cervical cancer? Ann Diagn Pathol. 17:305–311. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Zhang Z, Zhou D, Lai Y, Liu Y, Tao X, Wang Q, Zhao G, Gu H, Liao H, Zhu Y, et al: Estrogen induces endometrial cancer cell proliferation and invasion by regulating the fat mass and obesity-associated gene via PI3K/AKT and MAPK signaling pathways. Cancer Lett. 319:89–97. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Salani B, Del Rio A, Marini C, Sambuceti G, Cordera R and Maggi D: Metformin, cancer and glucose metabolism. Endocr Relat Cancer. 21:R461–R471. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Salani B, Marini C, Rio AD, Ravera S, Massollo M, Orengo AM, Amaro A, Passalacqua M, Maffioli S, Pfeffer U, et al: Metformin impairs glucose consumption and survival in Calu-1 cells by direct inhibition of hexokinase-II. Sci Rep. 3:20702013. View Article : Google Scholar : PubMed/NCBI

37 

Semenza GL: Hypoxia-inducible factor 1 (HIF-1) pathway. Sci STKE. 2007:cm82007. View Article : Google Scholar : PubMed/NCBI

38 

Roberts DJ, Tan-Sah VP, Smith JM and Miyamoto S: Akt phosphorylates HK-II at Thr-473 and increases mitochondrial HK-II association to protect cardiomyocytes. J Biol Chem. 288:23798–23806. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Marini C, Salani B, Massollo M, Amaro A, Esposito AI, Orengo AM, Capitanio S, Emionite L, Riondato M, Bottoni G, et al: Direct inhibition of hexokinase activity by metformin at least partially impairs glucose metabolism and tumor growth in experimental breast cancer. Cell Cycle. 12:3490–3499. 2013. View Article : Google Scholar : PubMed/NCBI

40 

Peng G-Q, Yang Y, Zhong C-G, Yin H, Hu G and Tian Y: A study of association between expression of hOGG1, VDAC1, HK-2 and cervical carcinoma. J Exp Clin Cancer Res. 29:1292010. View Article : Google Scholar

41 

Jin Z, Gu J, Xin X, Li Y and Wang H: Expression of hexokinase 2 in epithelial ovarian tumors and its clinical significance in serous ovarian cancer. Eur J Gynaecol Oncol. 35:519–524. 2014.PubMed/NCBI

42 

Huang X, Liu M, Sun H, Wang F, Xie X, Chen X, Su J, He Y, Dai Y, Wu H, et al: HK2 is a radiation resistant and independent negative prognostic factor for patients with locally advanced cervical squamous cell carcinoma. Int J Clin Exp Pathol. 8:4054–4063. 2015.PubMed/NCBI

43 

Husseinzadeh N and Husseinzadeh HD: mTOR inhibitors and their clinical application in cervical, endometrial and ovarian cancers: A critical review. Gynecol Oncol. 133:375–381. 2014. View Article : Google Scholar : PubMed/NCBI

44 

Li Y, Padmanabha D, Gentile LB, Dumur CI, Beckstead RB and Baker KD: HIF- and non-HIF-regulated hypoxic responses require the estrogen-related receptor in Drosophila melanogaster. PLoS Genet. 9:e10032302013. View Article : Google Scholar : PubMed/NCBI

45 

Fraga A, Ribeiro R and Medeiros R: Tumor hypoxia: The role of HIF. Actas Urol Esp. 33:941–951. 2009.In Spanish. View Article : Google Scholar : PubMed/NCBI

46 

Pitroda SP, Wakim BT, Sood RF, Beveridge MG, Beckett MA, MacDermed DM, Weichselbaum RR and Khodarev NN: STAT1-dependent expression of energy metabolic pathways links tumour growth and radioresistance to the Warburg effect. BMC Med. 7:682009. View Article : Google Scholar : PubMed/NCBI

47 

Hirschhaeuser F, Sattler UG and Mueller-Klieser W: Lactate: A metabolic key player in cancer. Cancer Res. 71:6921–6925. 2011. View Article : Google Scholar : PubMed/NCBI

48 

Shimura T, Noma N, Sano Y, Ochiai Y, Oikawa T, Fukumoto M and Kunugita N: AKT-mediated enhanced aerobic glycolysis causes acquired radioresistance by human tumor cells. Radiother Oncol. 112:302–307. 2014. View Article : Google Scholar : PubMed/NCBI

49 

Moeller BJ, Richardson RA and Dewhirst MW: Hypoxia and radiotherapy: Opportunities for improved outcomes in cancer treatment. Cancer Metastasis Rev. 26:241–248. 2007. View Article : Google Scholar : PubMed/NCBI

50 

Cullis PM, Jones GD, Symons MC and Lea JS: Electron transfer from protein to DNA in irradiated chromatin. Nature. 330:773–774. 1987. View Article : Google Scholar : PubMed/NCBI

51 

Bhatt AN, Chauhan A, Khanna S, Rai Y, Singh S, Soni R, Kalra N and Dwarakanath BS: Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells. BMC Cancer. 15:3352015. View Article : Google Scholar : PubMed/NCBI

52 

Pathania D, Millard M and Neamati N: Opportunities in discovery and delivery of anticancer drugs targeting mitochondria and cancer cell metabolism. Adv Drug Deliv Rev. 61:1250–1275. 2009. View Article : Google Scholar : PubMed/NCBI

53 

Deng Q, Yu X, Xiao L, Hu Z, Luo X, Tao Y, Yang L, Liu X, Chen H, Ding Z, et al: Neoalbaconol induces energy depletion and multiple cell death in cancer cells by targeting PDK1-PI3-K/Akt signaling pathway. Cell Death Dis. 4:e8042013. View Article : Google Scholar : PubMed/NCBI

54 

Roden R and Wu TC: How will HPV vaccines affect cervical cancer? Nat Rev Cancer. 6:753–763. 2006. View Article : Google Scholar : PubMed/NCBI

55 

Doorbar J: Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci (Lond). 110:525–541. 2006. View Article : Google Scholar

56 

Münger K, Basile JR, Duensing S, Eichten A, Gonzalez SL, Grace M and Zacny VL: Biological activities and molecular targets of the human papillomavirus E7 oncoprotein. Oncogene. 20:7888–7898. 2001. View Article : Google Scholar : PubMed/NCBI

57 

Rodolico V, Arancio W, Amato MC, Aragona F, Cappello F, Di Fede O, Pannone G and Campisi G: Hypoxia inducible factor-1 alpha expression is increased in infected positive HPV16 DNA oral squamous cell carcinoma and positively associated with HPV16 E7 oncoprotein. Infect Agent Cancer. 6:182011. View Article : Google Scholar : PubMed/NCBI

58 

Bodily JM, Mehta KP and Laimins LA: Human papillomavirus E7 enhances hypoxia-inducible factor 1-mediated transcription by inhibiting binding of histone deacetylases. Cancer Res. 71:1187–1195. 2011. View Article : Google Scholar

59 

Nakamura M, Bodily JM, Beglin M, Kyo S, Inoue M and Laimins LA: Hypoxia-specific stabilization of HIF-1alpha by human papillomaviruses. Virology. 387:442–448. 2009. View Article : Google Scholar : PubMed/NCBI

60 

Li G, He L, Zhang E, Shi J, Zhang Q, Le AD, Zhou K and Tang X: Overexpression of human papillomavirus (HPV) type 16 oncoproteins promotes angiogenesis via enhancing HIF-1α and VEGF expression in non-small cell lung cancer cells. Cancer Lett. 311:160–170. 2011. View Article : Google Scholar : PubMed/NCBI

61 

Gao JL and Chen YG: Natural compounds regulate glycolysis in hypoxic tumor microenvironment. BioMed Res Int. 2015:3541432015. View Article : Google Scholar : PubMed/NCBI

62 

Marín-Hernández A, Gallardo-Pérez JC, Ralph SJ, Rodríguez-Enríquez S and Moreno-Sánchez R: HIF-1alpha modulates energy metabolism in cancer cells by inducing overexpression of specific glycolytic isoforms. Mini Rev Med Chem. 9:1084–1101. 2009. View Article : Google Scholar

63 

Wang L, Xiong H, Wu F, Zhang Y, Wang J, Zhao L, Guo X, Chang LJ, Zhang Y, You MJ, et al: Hexokinase 2-mediated Warburg effect is required for PTEN- and p53-deficiency-driven prostate cancer growth. Cell Rep. 8:1461–1474. 2014. View Article : Google Scholar : PubMed/NCBI

64 

Zhuo B, Li Y, Li Z, Qin H, Sun Q, Zhang F, Shen Y, Shi Y and Wang R: PI3K/Akt signaling mediated Hexokinase-2 expression inhibits cell apoptosis and promotes tumor growth in pediatric osteosarcoma. Biochem Biophys Res Commun. 464:401–406. 2015. View Article : Google Scholar : PubMed/NCBI

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Spandidos Publications style
Liu Y, Murray-Stewart T, Casero RA, Kagiampakis I, Jin L, Zhang J, Wang H, Che Q, Tong H, Ke J, Ke J, et al: Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth. Int J Oncol 50: 2011-2023, 2017.
APA
Liu, Y., Murray-Stewart, T., Casero, R.A., Kagiampakis, I., Jin, L., Zhang, J. ... Wan, X. (2017). Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth. International Journal of Oncology, 50, 2011-2023. https://doi.org/10.3892/ijo.2017.3979
MLA
Liu, Y., Murray-Stewart, T., Casero, R. A., Kagiampakis, I., Jin, L., Zhang, J., Wang, H., Che, Q., Tong, H., Ke, J., Jiang, F., Wang, F., Wan, X."Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth". International Journal of Oncology 50.6 (2017): 2011-2023.
Chicago
Liu, Y., Murray-Stewart, T., Casero, R. A., Kagiampakis, I., Jin, L., Zhang, J., Wang, H., Che, Q., Tong, H., Ke, J., Jiang, F., Wang, F., Wan, X."Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth". International Journal of Oncology 50, no. 6 (2017): 2011-2023. https://doi.org/10.3892/ijo.2017.3979
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Spandidos Publications style
Liu Y, Murray-Stewart T, Casero RA, Kagiampakis I, Jin L, Zhang J, Wang H, Che Q, Tong H, Ke J, Ke J, et al: Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth. Int J Oncol 50: 2011-2023, 2017.
APA
Liu, Y., Murray-Stewart, T., Casero, R.A., Kagiampakis, I., Jin, L., Zhang, J. ... Wan, X. (2017). Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth. International Journal of Oncology, 50, 2011-2023. https://doi.org/10.3892/ijo.2017.3979
MLA
Liu, Y., Murray-Stewart, T., Casero, R. A., Kagiampakis, I., Jin, L., Zhang, J., Wang, H., Che, Q., Tong, H., Ke, J., Jiang, F., Wang, F., Wan, X."Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth". International Journal of Oncology 50.6 (2017): 2011-2023.
Chicago
Liu, Y., Murray-Stewart, T., Casero, R. A., Kagiampakis, I., Jin, L., Zhang, J., Wang, H., Che, Q., Tong, H., Ke, J., Jiang, F., Wang, F., Wan, X."Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth". International Journal of Oncology 50, no. 6 (2017): 2011-2023. https://doi.org/10.3892/ijo.2017.3979
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