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Article

Combination of Taxol® and dichloroacetate results in synergistically inhibitory effects on Taxol-resistant oral cancer cells under hypoxia

  • Authors:
    • Qi  Xie
    • Han‑Fang  Zhang
    • Ying‑Zi  Guo
    • Peng‑Yi  Wang
    • Zhong‑Shung  Liu
    • Hua‑Dong  Gao
    • Wei‑Li  Xie
  • View Affiliations / Copyright

    Affiliations: Department of Prosthodontics, School of Stomatology, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Institute of Hard Tissue Development and Regeneration, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
  • Pages: 2935-2940
    |
    Published online on: December 11, 2014
       https://doi.org/10.3892/mmr.2014.3080
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Abstract

Cancer cells preferentially catalyze glucose through the glycolytic pathway in the presence of adequate oxygen. This phenomenon is known as the Warburg effect. As is the case with numerous cancer therapeutic agents, resistance remains a significant problem when using Taxol® to treat malignancies. The present study reported that expression of pyruvate dehydrogenase kinase 1 (PDK1) was induced by Taxol treatment at low toxic concentrations in oral cancer cells. In addition, Taxol‑resistant cells exhibited upregulated PDK1 protein and mRNA expression. Elevated PDK1 levels contribute to Taxol resistance under hypoxic conditions. Inhibition of PDK1 expression was observed when oral cancer cells were treated with the PDK1 inhibitor dichloroacetate (DCA). The combination of Taxol with DCA showed synergistic inhibitory effects on Taxol‑resistant cells under hypoxic conditions; these effects were not observed in Taxol‑sensitive oral cancer cells under normoxic conditions. The present study provides a novel mechanism for overcoming Taxol resistance in oral cancer cells, and will contribute towards the development of clinical therapeutics for cancer patients.
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1 

Orr GA, Verdier-Pinard P, McDaid H and Horwitz SB: Mechanisms of Taxol resistance related to microtubules. Oncogene. 22:7280–7295. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Marcus AI, Peters U, Thomas SL, et al: Mitotic kinesin inhibitors induce mitotic arrest and cell death in Taxol-resistant and -sensitive cancer cells. J Biol Chem. 280:11569–11577. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Yang YI, Lee KT, Park HJ, et al: Tectorigenin sensitizes paclitaxel-resistant human ovarian cancer cells through downregulation of the Akt and NFκB pathway. Carcinogenesis. 33:2488–2498. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Lai D, Ho KC, Hao Y and Yang X: Taxol resistance in breast cancer cells is mediated by the hippo pathway component TAZ and its downstream transcriptional targets Cyr61 and CTGF. Cancer Res. 71:2728–2738. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Ledwitch K, Ogburn R, Cox J, et al: Taxol: efficacy against oral squamous cell carcinoma. Mini Rev Med Chem. 13:509–521. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Xu R, Sato N, Yanai K, et al: Enhancement of paclitaxel-induced apoptosis by inhibition of mitogen-activated protein kinase pathway in colon cancer cells. Anticancer Res. 29:261–270. 2009.PubMed/NCBI

7 

Groen HJ, Fokkema E, Biesma B, et al: Paclitaxel and carboplatin in the treatment of small-cell lung cancer patients resistant to cyclophosphamide, doxorubicin, and etoposide: a non-cross-resistant schedule. J Clin Oncol. 17:927–932. 1999.PubMed/NCBI

8 

González Cao M, Viteri S, Garrán C, et al: Response of resistant melanoma to a combination of weekly paclitaxel and bevacizumab. Clin Transl Oncol. 9:119–120. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Yusuf RZ, Duan Z, Lamendola DE, Penson RT and Seiden MV: Paclitaxel resistance: molecular mechanisms and pharmacologic manipulation. Curr Cancer Drug Targets. 3:1–19. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Gottesman MM and Pastan I: Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem. 62:385–427. 1993. View Article : Google Scholar : PubMed/NCBI

11 

Kavallaris M, Kuo DY, Burkhart CA, et al: Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J Clin Invest. 100:1282–1293. 1997. View Article : Google Scholar : PubMed/NCBI

12 

Panda D, Miller HP, Banerjee A, Ludueña RF and Wilson L: Microtubule dynamics in vitro are regulated by the tubulin isotype composition. Proc Natl Acad Sci USA. 91:11358–11362. 1994. View Article : Google Scholar : PubMed/NCBI

13 

Martello LA, Verdier-Pinard P, Shen HJ, et al: Elevated levels of microtubule destabilizing factors in a Taxol-resistant/dependent A549 cell line with an alpha-tubulin mutation. Cancer Res. 63:1207–1213. 2003.PubMed/NCBI

14 

Gonçalves A, Braguer D, Kamath K, et al: Resistance to Taxol in lung cancer cells associated with increased microtubule dynamics. Proc Natl Acad Sci USA. 98:11737–11742. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Tan M, Jing T, Lan KH, et al: Phosphorylation on tyrosine-15 of p34(Cdc2) by ErbB2 inhibits p34(Cdc2) activation and is involved in resistance to taxol-induced apoptosis. Mol Cell. 9:993–1004. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Lu J, Tan M, Huang WC, et al: Mitotic deregulation by survivin in ErbB2-overexpressing breast cancer cells contributes to Taxol resistance. Clin Cancer Res. 15:1326–1334. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Warburg O: On respiratory impairment in cancer cells. Science. 124:269–270. 1956.PubMed/NCBI

18 

Jang M, Kim SS and Lee J: Cancer cell metabolism: implications for therapeutic targets. Exp Mol Med. 45:e452013. View Article : Google Scholar : PubMed/NCBI

19 

Saed GM, Fletcher NM, Jiang ZL, et al: Dichloroacetate induces apoptosis of epithelial ovarian cancer cells through a mechanism involving modulation of oxidative stress. Reprod Sci. 18:1253–1261. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Sutendra G and Michelakis ED: Pyruvate dehydrogenase kinase as a novel therapeutic target in oncology. Front Oncol. 3:382013. View Article : Google Scholar : PubMed/NCBI

21 

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

22 

Fujiwara S, Kawano Y, Yuki H, et al: PDK1 inhibition is a novel therapeutic target in multiple myeloma. Br J Cancer. 108:170–178. 2013.PubMed/NCBI

23 

Zhao Y, Butler EB and Tan M: Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis. 4:e5322013. View Article : Google Scholar : PubMed/NCBI

24 

Fulda S and Debatin KM: HIF-1-regulated glucose metabolism: a key to apoptosis resistance? Cell Cycle. 6:790–792. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Zhou M, Zhao Y, Ding Y, et al: Warburg effect in chemosensitivity: targeting lactate dehydrogenase-A re-sensitizes taxol-resistant cancer cells to taxol. Mol Cancer. 9:332010. View Article : Google Scholar : PubMed/NCBI

26 

Bryan M, Pulte ED, Toomey KC, et al: A pilot phase II trial of all-trans retinoic acid (Vesanoid) and paclitaxel (Taxol) in patients with recurrent or metastatic breast cancer. Invest New Drugs. 29:1482–1487. 2011. View Article : Google Scholar

27 

Ishibashi M, Nakayama K, Yeasmin S, et al: A BTB/POZ gene, NAC-1, a tumor recurrence-associated gene, as a potential target for Taxol resistance in ovarian cancer. Clin Cancer Res. 14:3149–3155. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Wang X, Pan L, Mao N, et al: Cell-cycle synchronization reverses Taxol resistance of human ovarian cancer cell lines. Cancer Cell Int. 13:772013. View Article : Google Scholar : PubMed/NCBI

29 

Ding Y, Liu Z, Desai S, et al: Receptor tyrosine kinase ErbB2 translocates into mitochondria and regulates cellular metabolism. Nat Commun. 3:12712012. View Article : Google Scholar : PubMed/NCBI

30 

Zheng J: Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review). Oncol Lett. 4:1151–1157. 2012.PubMed/NCBI

31 

Elstrom RL, Bauer DE, Buzzai M, et al: Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 64:3892–3899. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Fan Y, Dickman KG and Zong WX: Akt and c-Myc differentially activate cellular metabolic programs and prime cells to bioenergetic inhibition. J Biol Chem. 285:7324–7333. 2010. View Article : Google Scholar :

33 

Kim JW, Tchernyshyov I, Semenza GL and Dang CV: HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 3:177–185. 2006. View Article : Google Scholar : PubMed/NCBI

34 

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. 102:1746–1752. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Michelakis ED, Sutendra G, Dromparis P, et al: Metabolic modulation of glioblastoma with dichloroacetate. Sci Transl Med. 2:31ra342010. View Article : Google Scholar : PubMed/NCBI

36 

Kato M, Li J, Chuang JL and Chuang DT: Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol. Structure. 15:992–1004. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Xie Q, Zhang HF, Guo YZ, Wang PY, Liu ZS, Gao HD and Xie WL: Combination of Taxol® and dichloroacetate results in synergistically inhibitory effects on Taxol-resistant oral cancer cells under hypoxia. Mol Med Rep 11: 2935-2940, 2015.
APA
Xie, Q., Zhang, H., Guo, Y., Wang, P., Liu, Z., Gao, H., & Xie, W. (2015). Combination of Taxol® and dichloroacetate results in synergistically inhibitory effects on Taxol-resistant oral cancer cells under hypoxia. Molecular Medicine Reports, 11, 2935-2940. https://doi.org/10.3892/mmr.2014.3080
MLA
Xie, Q., Zhang, H., Guo, Y., Wang, P., Liu, Z., Gao, H., Xie, W."Combination of Taxol® and dichloroacetate results in synergistically inhibitory effects on Taxol-resistant oral cancer cells under hypoxia". Molecular Medicine Reports 11.4 (2015): 2935-2940.
Chicago
Xie, Q., Zhang, H., Guo, Y., Wang, P., Liu, Z., Gao, H., Xie, W."Combination of Taxol® and dichloroacetate results in synergistically inhibitory effects on Taxol-resistant oral cancer cells under hypoxia". Molecular Medicine Reports 11, no. 4 (2015): 2935-2940. https://doi.org/10.3892/mmr.2014.3080
Copy and paste a formatted citation
x
Spandidos Publications style
Xie Q, Zhang HF, Guo YZ, Wang PY, Liu ZS, Gao HD and Xie WL: Combination of Taxol® and dichloroacetate results in synergistically inhibitory effects on Taxol-resistant oral cancer cells under hypoxia. Mol Med Rep 11: 2935-2940, 2015.
APA
Xie, Q., Zhang, H., Guo, Y., Wang, P., Liu, Z., Gao, H., & Xie, W. (2015). Combination of Taxol® and dichloroacetate results in synergistically inhibitory effects on Taxol-resistant oral cancer cells under hypoxia. Molecular Medicine Reports, 11, 2935-2940. https://doi.org/10.3892/mmr.2014.3080
MLA
Xie, Q., Zhang, H., Guo, Y., Wang, P., Liu, Z., Gao, H., Xie, W."Combination of Taxol® and dichloroacetate results in synergistically inhibitory effects on Taxol-resistant oral cancer cells under hypoxia". Molecular Medicine Reports 11.4 (2015): 2935-2940.
Chicago
Xie, Q., Zhang, H., Guo, Y., Wang, P., Liu, Z., Gao, H., Xie, W."Combination of Taxol® and dichloroacetate results in synergistically inhibitory effects on Taxol-resistant oral cancer cells under hypoxia". Molecular Medicine Reports 11, no. 4 (2015): 2935-2940. https://doi.org/10.3892/mmr.2014.3080
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