Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
September-2018 Volume 42 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2018 Volume 42 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Reversal of the Warburg effect with DCA in PDGF‑treated human PASMC is potentiated by pyruvate dehydrogenase kinase‑1 inhibition mediated through blocking Akt/GSK‑3β signalling

  • Authors:
    • Bingbing Li
    • Yuling Zhu
    • Qing Sun
    • Chunfang Yu
    • Lian Chen
    • Yali Tian
    • Jie Yan
  • View Affiliations / Copyright

    Affiliations: Department of Anaesthesiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China, Department of Anaesthesiology, The Affiliated Obstetrics and Gynaecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1391-1400
    |
    Published online on: June 27, 2018
       https://doi.org/10.3892/ijmm.2018.3745
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

There is accumulating evidence indicating that the growth inhibitory effect of dichloroacetate (DCA) on pulmonary arterial smooth muscle cells (PASMCs) may be associated with the reversal of the Warburg effect and initiation of the mitochondria‑dependent apoptotic pathway. Previous studies indicated that platelet‑derived growth factor (PDGF) promoted the Warburg effect and resulted in apoptotic resistance of PASMCs, which was attributed to activation of the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) signalling pathway. However, the mechanism underlying the pro‑apoptotic effect of DCA on PDGF‑treated PASMCs has not been thoroughly elucidated, and the effect of the Akt/glycogen synthase kinase‑3β (GSK‑3β) pathway inhibition concomitant with the effect of DCA on PASMC proliferation remains unclear. The growth of human PASMCs and the lactate concentration in extracellular medium of PASMCs were detected by Cell Counting Kit‑8 assays and a Lactate Colorimetric Assay kit, respectively. Cell apoptosis was evaluated by fluorescence activated cell sorting. The mitochondrial membrane potential (ΔΨm) was assessed with 5,5',6,6'‑tetrachloro‑1,1',3,3'‑tetraethylbenzimidazol‑carbocyanine iodide assays. The expression levels of phosphorylated Akt and GSK‑3β, pyruvate dehydrogenase, cleaved caspase‑3, pyruvate dehydrogenase kinase‑1 (PDK‑1), hypoxia inducible factor‑1α (HIF‑1α) and hexokinase‑2 (HK‑2) were measured with western blot analysis. Confocal analyses were employed to determine HK‑2 co‑localisation with the mitochondria. The results indicated that DCA inhibited human PASMC proliferation in a dose‑dependent manner. DCA at 10 mM promoted apoptosis and the upregulation of activated caspase‑3 in PASMCs pre‑treated with 20 ng/ml PDGF‑homeodimer BB (BB). Treatment with 5 µM LY294002 produced minimal anti‑proliferative effects on human PASMCs and barely induced cellular apoptosis and caspase‑3 activation. However, co‑administration of 10 mM DCA with LY294002 significantly decreased the cell proliferation index and induced cell apoptosis and caspase‑3 activation. The combined administration of LY294002 with DCA significantly decreased lactate concentration, promoted the depolarisation of the ΔΨm and repressed HIF‑1α upregulation and HK‑2 activation in PASMCs treated with PDGF, which was attributed to the potentiation of DCA‑induced PDK‑1 inhibition by LY294002 via blockade of the Akt/GSK‑3β/HIF‑1α signalling pathway. In conclusion, inhibition of the Akt/GSK‑3β pathway improved the pro‑apoptotic effect of DCA on human PASMCs, which may be attributed to a reversal of the Warburg effect by blocking the mutual interaction between HIF‑1α and PDK‑1, consequently downregulating HK‑2. Therefore, combinatory treatment with DCA and PI3K inhibitors may represent a novel therapeutic strategy for the reversal of apoptosis resistance exhibited by PASMCs as a result of mitochondrial bioenergetic abnormalities, as well as the treatment of pulmonary vascular remodelling in pulmonary arterial hypertension.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Gurtu V and Michelakis ED: Emerging therapies and future directions in pulmonary arterial hypertension. Can J Cardiol. 31:489–501. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Tuder RM: Pathology of pulmonary arterial hypertension. Semin Respir Crit Care Med. 30:376–385. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Michelakis ED, Webster L and Mackey JR: Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Br J Cancer. 99:989–994. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Paulin R and Michelakis ED: The metabolic theory of pulmonary arterial hypertension. Circ Res. 115:148–164. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, et al: Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest. 115:2811–2821. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Berghausen E, ten Freyhaus H and Rosenkranz S: Targeting of platelet-derived growth factor signaling in pulmonary arterial hypertension. Handb Exp Pharmacol. 218:381–408. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Xiao Y, Peng H, Hong C, Chen Z, Deng X, Wang A, Yang F, Yang L, Chen C and Qin X: PDGF promotes the warburg effect in pulmonary arterial smooth muscle cells via activation of the PI3K/AKT/mTOR/HIF-1α signaling pathway. Cell Physiol Biochem. 42:1603–1613. 2017. View Article : Google Scholar

8 

Rehman J and Archer SL: A proposed mitochondrial-metabolic mechanism for initiation and maintenance of pulmonary arterial hypertension in fawn-hooded rats: The Warburg model of pulmonary arterial hypertension. Adv Exp Med Biol. 661:171–185. 2010. View Article : Google Scholar : PubMed/NCBI

9 

McMurtry MS, Bonnet S, Wu X, Dyck JR, Haromy A, Hashimoto K and Michelakis ED: Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res. 95:830–840. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Guignabert C, Tu L, Izikki M, Dewachter L, Zadigue P, Humbert M, Adnot S, Fadel E and Eddahibi S: Dichloroacetate treatment partially regresses established pulmonary hypertension in mice with SM22alpha-targeted overexpression of the serotonin transporter. FASEB J. 23:4135–4147. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Michelakis ED, McMurtry MS, Wu XC, Dyck JR, Moudgil R, Hopkins TA, Lopaschuk GD, Puttagunta L, Waite R and Archer SL: Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: Role of increased expression and activity of voltage-gated potassium channels. Circulation. 105:244–250. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Lambert CM, Roy M, Robitaille GA, Richard DE and Bonnet S: HIF-1 inhibition decreases systemic vascular remodelling diseases by promoting apoptosis through a hexokinase 2-dependent mechanism. Cardiovasc Res. 88:196–204. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Semenza GL: Hypoxia-inducible factor 1: Oxygen homeostasis and disease pathophysiology. Trends Mol Med. 7:345–350. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Wilson JE: Isozymes of mammalian hexokinase. Structure, subcellular localization and metabolic function. J Exp Biol. 206:2049–2057. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Pastorino JG and Hoek JB: Hexokinase II: The integration of energy metabolism and control of apoptosis. Curr Med Chem. 10:1535–1551. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Yasuda S, Arii S, Mori A, Isobe N, Yang W, Oe H, Fujimoto A, Yonenaga Y, Sakashita H and Imamura M: Hexokinase II and VEGF expression in liver tumors: Correlation with hypoxia-inducible factor 1 alpha and its significance. J Hepatol. 40:117–123. 2004. View Article : Google Scholar

17 

Riddle SR, Ahmad A, Ahmad S, Deeb SS, Malkki M, Schneider BK, Allen CB and White CW: Hypoxia induces hexokinase II gene expression in human lung cell line A549. Am J Physiol Lung Cell Mol Physiol. 278:L407–L416. 2000. View Article : Google Scholar : PubMed/NCBI

18 

Yan J, Shen Y, Wang Y and Li BB: Increased expression of hypoxia-inducible factor-1α in proliferating neointimal lesions in a rat model of pulmonary arterial hypertension. Am J Med Sci. 345:121–128. 2013. View Article : Google Scholar

19 

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

20 

Bonnet S, Paulin R, Sutendra G, Dromparis P, Roy M, Watson KO, Nagendran J, Haromy A, Dyck JR and Michelakis ED: Dehydroepiandrosterone reverses systemic vascular remodeling through the inhibition of the Akt/GSK3-{beta}/NFAT axis. Circulation. 120:1231–1240. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Dromparis P, Sutendra G and Michelakis ED: The role of mitochondria in pulmonary vascular remodeling. J Mol Med. 88:1003–1010. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Assad TR and Hemnes AR: Metabolic dysfunction in pulmonary arterial hypertension. Curr Hypertens Rep. 17:202015. View Article : Google Scholar : PubMed/NCBI

23 

Haugrud AB, Zhuang Y, Coppock JD and Miskimins WK: Dichloroacetate enhances apoptotic cell death via oxidative damage and attenuates lactate production in metformin-treated breast cancer cells. Breast Cancer Res Treat. 147:539–550. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Allen KT, Chin-Sinex H, DeLuca T, Pomerening JR, Sherer J, Watkins JB III, Foley J, Jesseph JM and Mendonca MS: Dichloroacetate alters Warburg metabolism, inhibits cell growth, and increases the X-ray sensitivity of human A549 and H1299 NSC lung cancer cells. Free Radic Biol Med. 89:263–273. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Antoniu SA: Targeting PDGF pathway in pulmonary arterial hypertension. Expert Opin Ther Targets. 16:1055–1063. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Peng H, Xiao Y, Deng X, Luo J, Hong C and Qin X: The Warburg effect: A new story in pulmonary arterial hypertension. Clin Chim Acta. 461:53–58. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Bonnet S, Michelakis ED, Porter CJ, Andrade-Navarro MA, Thébaud B, Bonnet S, Haromy A, Harry G, Moudgil R, McMurtry MS, et al: An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: Similarities to human pulmonary arterial hypertension. Circulation. 113:2630–2641. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Wong JY, Huggins GS, Debidda M, Munshi NC and De Vivo I: Dichloroacetate induces apoptosis in endometrial cancer cells. Gynecol Oncol. 109:394–402. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Madhok BM, Yeluri S, Perry SL, Hughes TA and Jayne DG: Dichloroacetate induces apoptosis and cell-cycle arrest in colorectal cancer cells. Br J Cancer. 102:1746–17521. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Sun RC, Board PG and Blackburn AC: Targeting metabolism with arsenic trioxide and dichloroacetate in breast cancer cells. Mol Cancer. 10:1422011. View Article : Google Scholar : PubMed/NCBI

31 

Stacpoole PW, Nagaraja NV and Hutson AD: Efficacy of dichloroacetate as a lactate-lowering drug. J Clin Pharmacol. 43:683–691. 2003. View Article : Google Scholar : PubMed/NCBI

32 

Kagiava A and Theophilidis G: High concentrations of dichloroacetate have minor effects on the vitality of the mammalian nerve fibers: An ex-vivo electrophysiological study. Anticancer Drugs. 22:273–276. 2011. View Article : Google Scholar

33 

Cao W, Yacoub S, Shiverick KT, Namiki K, Sakai Y, Porvasnik S, Urbanek C and Rosser CJ: Dichloroacetate (DCA) sensitizes both wild-type and over expressing Bcl-2 prostate cancer cells in vitro to radiation. Prostate. 68:1223–1231. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Tong J, Xie G, He J, Li J, Pan F and Liang H: Synergistic antitumor effect of dichloroacetate in combination with 5-fluorouracil in colorectal cancer. J Biomed Biotechnol. 2011:7405642011. View Article : Google Scholar : PubMed/NCBI

35 

Wang H, Wang L, Zhang Y, Wang J, Deng Y and Lin D: Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth. Cancer Cell Int. 16:92016. View Article : Google Scholar : PubMed/NCBI

36 

Ahn KJ, Hwang HS, Park JH, Bang SH, Kang WJ, Yun M and Lee JD: Evaluation of the role of hexokinase type II in cellular proliferation and apoptosis using human hepatocellular carcinoma cell lines. J Nucl Med. 50:1525–1532. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Masoud GN and Li W: HIF-1α pathway: Role, regulation and intervention for cancer therapy. Acta Pharm Sin B. 5:378–389. 2015. View Article : Google Scholar : PubMed/NCBI

38 

Semenza GL: HIF-1: Upstream and downstream of cancer metabolism. Curr Opin Genet Dev. 20:51–56. 2010. View Article : Google Scholar :

39 

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

40 

Perez J, Hill BG, Benavides GA, Dranka BP and Darley-Usmar VM: Role of cellular bioenergetics in smooth muscle cell proliferation induced by platelet-derived growth factor. Biochem J. 428:255–267. 2010. View Article : Google Scholar : PubMed/NCBI

41 

Cerniglia GJ, Dey S, Gallagher-Colombo SM, Daurio NA, Tuttle S, Busch TM, Lin A, Sun R, Esipova TV, Vinogradov SA, et al: The PI3K/Akt pathway regulates oxygen metabolism via pyruvate dehydrogenase (PDH)-E1α phosphorylation. Mol Cancer Ther. 14:1928–1938. 2015. View Article : Google Scholar : PubMed/NCBI

42 

Yang X, Cheng Y, Li P, Tao J, Deng X, Zhang X, Gu M, Lu Q and Yin C: A lentiviral sponge for miRNA-21 diminishes aerobic glycolysis in bladder cancer T24 cells via the PTEN/PI3K/AKT/mTOR axis. Tumour Biol. 36:383–391. 2015. View Article : Google Scholar

43 

Delaney LM, Ho N, Morrison J, Farias NR, Mosser DD and Coomber BL: Dichloroacetate affects proliferation but not survival of human colorectal cancer cells. Apoptosis. 20:63–74. 2015. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li B, Zhu Y, Sun Q, Yu C, Chen L, Tian Y and Yan J: Reversal of the Warburg effect with DCA in PDGF‑treated human PASMC is potentiated by pyruvate dehydrogenase kinase‑1 inhibition mediated through blocking Akt/GSK‑3β signalling. Int J Mol Med 42: 1391-1400, 2018.
APA
Li, B., Zhu, Y., Sun, Q., Yu, C., Chen, L., Tian, Y., & Yan, J. (2018). Reversal of the Warburg effect with DCA in PDGF‑treated human PASMC is potentiated by pyruvate dehydrogenase kinase‑1 inhibition mediated through blocking Akt/GSK‑3β signalling. International Journal of Molecular Medicine, 42, 1391-1400. https://doi.org/10.3892/ijmm.2018.3745
MLA
Li, B., Zhu, Y., Sun, Q., Yu, C., Chen, L., Tian, Y., Yan, J."Reversal of the Warburg effect with DCA in PDGF‑treated human PASMC is potentiated by pyruvate dehydrogenase kinase‑1 inhibition mediated through blocking Akt/GSK‑3β signalling". International Journal of Molecular Medicine 42.3 (2018): 1391-1400.
Chicago
Li, B., Zhu, Y., Sun, Q., Yu, C., Chen, L., Tian, Y., Yan, J."Reversal of the Warburg effect with DCA in PDGF‑treated human PASMC is potentiated by pyruvate dehydrogenase kinase‑1 inhibition mediated through blocking Akt/GSK‑3β signalling". International Journal of Molecular Medicine 42, no. 3 (2018): 1391-1400. https://doi.org/10.3892/ijmm.2018.3745
Copy and paste a formatted citation
x
Spandidos Publications style
Li B, Zhu Y, Sun Q, Yu C, Chen L, Tian Y and Yan J: Reversal of the Warburg effect with DCA in PDGF‑treated human PASMC is potentiated by pyruvate dehydrogenase kinase‑1 inhibition mediated through blocking Akt/GSK‑3β signalling. Int J Mol Med 42: 1391-1400, 2018.
APA
Li, B., Zhu, Y., Sun, Q., Yu, C., Chen, L., Tian, Y., & Yan, J. (2018). Reversal of the Warburg effect with DCA in PDGF‑treated human PASMC is potentiated by pyruvate dehydrogenase kinase‑1 inhibition mediated through blocking Akt/GSK‑3β signalling. International Journal of Molecular Medicine, 42, 1391-1400. https://doi.org/10.3892/ijmm.2018.3745
MLA
Li, B., Zhu, Y., Sun, Q., Yu, C., Chen, L., Tian, Y., Yan, J."Reversal of the Warburg effect with DCA in PDGF‑treated human PASMC is potentiated by pyruvate dehydrogenase kinase‑1 inhibition mediated through blocking Akt/GSK‑3β signalling". International Journal of Molecular Medicine 42.3 (2018): 1391-1400.
Chicago
Li, B., Zhu, Y., Sun, Q., Yu, C., Chen, L., Tian, Y., Yan, J."Reversal of the Warburg effect with DCA in PDGF‑treated human PASMC is potentiated by pyruvate dehydrogenase kinase‑1 inhibition mediated through blocking Akt/GSK‑3β signalling". International Journal of Molecular Medicine 42, no. 3 (2018): 1391-1400. https://doi.org/10.3892/ijmm.2018.3745
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team