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Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target

  • Authors:
    • Hoon Hur
    • Yi Xuan
    • Young Bae Kim
    • Gwang Lee
    • Wooyoung Shim
    • Jisoo Yun
    • In-Hye Ham
    • Sang-Uk Han
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Ajou University School of Medicine, Suwon, Gyeonggi-do 443-749, Republic of Korea, Department of Pathology, Ajou University School of Medicine, Suwon, Gyeonggi-do 443-749, Republic of Korea, Institute for Gastric Cancer Mechanism, Ajou University School of Medicine, Suwon, Gyeonggi-do 443-749, Republic of Korea
    Copyright: © Hur et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 44-54
    |
    Published online on: November 6, 2012
       https://doi.org/10.3892/ijo.2012.1687
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Abstract

In contrast to mitochondria in healthy cells, which utilize oxidative phosphorylation, malignant cells undergo elevated glycolysis for energy production using glucose. The objectives of this study were to evaluate whether the expression of various molecules, including pyruvate dehydrogenase kinase-1 (PDK-1), is involved in the altered glucose metabolism associated with gastric cancer prognosis and to assess the role of a therapeutic agent in targeting glucose metabolism in gastric cancer. Immunohistochemistry was performed on gastric cancer tissues obtained from 152 patients who underwent curative resection to assess the expression of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), hexokinase-2 (HK-2) and PDK-1. In an in vitro analysis, the lactate production and glucose uptake levels, cellular viability and 5-fluorouracil (5-FU) responses were evaluated before and after treatment with dichloroacetate (DCA), a PDK-1 inhibitor, in the MKN45 and AGS gastric cancer cell lines and in the non-cancerous HEK293 cell line. GLUT-1 and PDK-1 expression was significantly associated with tumor progression, although only PDK-1 expression was an independent prognostic factor for patients who received 5-FU adjuvant treatment. There was no significant difference in cell viability between the HEK293 and gastric cancer cell lines following DCA treatment. However, DCA treatment reduced lactate production and increased responsiveness to 5-FU in MKN45 cells, which expressed high levels of PDK-1 in comparison to the other cell lines. Thus, PDK-1 may serve as a biomarker of poor prognosis in patients with gastric cancer. In addition, PDK-1 inhibitors such as DCA may be considered an additional treatment option for patients with PDK-1-expressing gastric cancers.
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View References

1. 

Jemal A, Siegel R, Ward E, Murray T, Xu J and Thun MJ: Cancer statistics, 2007. CA Cancer J Clin. 57:43–66. 2007. View Article : Google Scholar

2. 

An JY, Cheong JH, Hyung WJ and Noh SH: Recent evolution of surgical treatment for gastric cancer in Korea. J Gastric Cancer. 11:1–6. 2011. View Article : Google Scholar

3. 

Macdonald JS, Smalley SR, Benedetti J, et al: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 345:725–730. 2001. View Article : Google Scholar

4. 

Sakuramoto S, Sasako M, Yamaguchi T, et al: Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 357:1810–1820. 2007. View Article : Google Scholar : PubMed/NCBI

5. 

Denko NC: Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer. 8:705–713. 2008. View Article : Google Scholar : PubMed/NCBI

6. 

Park MJ, Lee WJ, Lim HK, Park KW, Choi JY and Kim BT: Detecting recurrence of gastric cancer: the value of FDG PET/CT. Abdom Imaging. 34:441–447. 2009. View Article : Google Scholar : PubMed/NCBI

7. 

Weber WA, Petersen V, Schmidt B, et al: Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use. J Clin Oncol. 21:2651–2657. 2003. View Article : Google Scholar : PubMed/NCBI

8. 

Wieder HA, Brucher BL, Zimmermann F, et al: Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment. J Clin Oncol. 22:900–908. 2004. View Article : Google Scholar : PubMed/NCBI

9. 

Madhok BM, Yeluri S, Perry SL, Hughes TA and Jayne DG: Targeting glucose metabolism: an emerging concept for anti-cancer therapy. Am J Clin Oncol. 34:628–635. 2011. View Article : Google Scholar : PubMed/NCBI

10. 

Kawamura T, Kusakabe T, Sugino T, et al: Expression of glucose transporter-1 in human gastric carcinoma: association with tumor aggressiveness, metastasis, and patient survival. Cancer. 92:634–641. 2001. View Article : Google Scholar : PubMed/NCBI

11. 

Noguchi Y, Marat D, Saito A, et al: Expression of facilitative glucose transporters in gastric tumors. Hepatogastroenterology. 46:2683–2689. 1999.PubMed/NCBI

12. 

Kaelin WG Jr and Thompson CB: Q&A: cancer: clues from cell metabolism. Nature. 465:562–564. 2010.

13. 

Egawa-Takata T, Endo H, Fujita M, et al: Early reduction of glucose uptake after cisplatin treatment is a marker of cisplatin sensitivity in ovarian cancer. Cancer Sci. 101:2171–2178. 2010. View Article : Google Scholar : PubMed/NCBI

14. 

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

15. 

Noske A, Kaszubiak A, Weichert W, et al: Specific inhibition of AKT2 by RNA interference results in reduction of ovarian cancer cell proliferation: increased expression of AKT in advanced ovarian cancer. Cancer Lett. 246:190–200. 2007. View Article : Google Scholar : PubMed/NCBI

16. 

Surowiak P, Materna V, Denkert C, et al: Significance of cyclooxygenase 2 and MDR1/P-glycoprotein coexpression in ovarian cancers. Cancer Lett. 235:272–280. 2006. View Article : Google Scholar : PubMed/NCBI

17. 

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

18. 

Holness MJ and Sugden MC: Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation. Biochem Soc Trans. 31:1143–1151. 2003. View Article : Google Scholar : PubMed/NCBI

19. 

Bowker-Kinley M and Popov KM: Evidence that pyruvate dehydrogenase kinase belongs to the ATPase/kinase superfamily. Biochem J. 344:47–53. 1999. View Article : Google Scholar : PubMed/NCBI

20. 

Popov KM: Regulation of mammalian pyruvate dehydrogenase kinase. FEBS Lett. 419:197–200. 1997. View Article : Google Scholar : PubMed/NCBI

21. 

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

22. 

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

23. 

Stacpoole PW: Review of the pharmacologic and therapeutic effects of diisopropylammonium dichloroacetate (DIPA). J Clin Pharmacol J New Drugs. 9:282–291. 1969.PubMed/NCBI

24. 

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

25. 

Sun RC, Fadia M, Dahlstrom JE, Parish CR, Board PG and Blackburn AC: Reversal of the glycolytic phenotype by dichloro-acetate inhibits metastatic breast cancer cell growth in vitro and in vivo. Breast Cancer Res Treat. 120:253–260. 2010. View Article : Google Scholar : PubMed/NCBI

26. 

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

27. 

Cao W, Yacoub S, Shiverick KT, et al: 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

28. 

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

29. 

Bonnet S, Archer SL, Allalunis-Turner J, et al: A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 11:37–51. 2007.

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Copy and paste a formatted citation
Spandidos Publications style
Hur H, Xuan Y, Kim YB, Lee G, Shim W, Yun J, Ham I and Han S: Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target. Int J Oncol 42: 44-54, 2013.
APA
Hur, H., Xuan, Y., Kim, Y.B., Lee, G., Shim, W., Yun, J. ... Han, S. (2013). Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target. International Journal of Oncology, 42, 44-54. https://doi.org/10.3892/ijo.2012.1687
MLA
Hur, H., Xuan, Y., Kim, Y. B., Lee, G., Shim, W., Yun, J., Ham, I., Han, S."Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target". International Journal of Oncology 42.1 (2013): 44-54.
Chicago
Hur, H., Xuan, Y., Kim, Y. B., Lee, G., Shim, W., Yun, J., Ham, I., Han, S."Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target". International Journal of Oncology 42, no. 1 (2013): 44-54. https://doi.org/10.3892/ijo.2012.1687
Copy and paste a formatted citation
x
Spandidos Publications style
Hur H, Xuan Y, Kim YB, Lee G, Shim W, Yun J, Ham I and Han S: Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target. Int J Oncol 42: 44-54, 2013.
APA
Hur, H., Xuan, Y., Kim, Y.B., Lee, G., Shim, W., Yun, J. ... Han, S. (2013). Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target. International Journal of Oncology, 42, 44-54. https://doi.org/10.3892/ijo.2012.1687
MLA
Hur, H., Xuan, Y., Kim, Y. B., Lee, G., Shim, W., Yun, J., Ham, I., Han, S."Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target". International Journal of Oncology 42.1 (2013): 44-54.
Chicago
Hur, H., Xuan, Y., Kim, Y. B., Lee, G., Shim, W., Yun, J., Ham, I., Han, S."Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target". International Journal of Oncology 42, no. 1 (2013): 44-54. https://doi.org/10.3892/ijo.2012.1687
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