Open Access

Inhibition of pyruvate dehydrogenase kinase‑1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming

  • Authors:
    • Huadan Xu
    • Yichun He
    • Jiaoyan Ma
    • Yuanxin Zhao
    • Yanan Liu
    • Liankun Sun
    • Jing Su
  • View Affiliations

  • Published online on: July 10, 2020     https://doi.org/10.3892/ijo.2020.5098
  • Pages: 733-742
  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The Warburg effect is a unique metabolic feature of the majority of tumor cells and is closely related to chemotherapeutic resistance. Pyruvate dehydrogenase kinase 1 (PDK1) is considered a ‘switch’ that controls the fate of pyruvate in glucose metabolism. However, to date, to the best of our knowledge, there are only a few studies to available which had studied the reduction of chemotherapeutic resistance via the metabolic reprogramming of tumor cells with PDK1 as a target. In the present study, it was found dicoumarol (DIC) reduced the phosphorylation of pyruvate dehydrogenase (PDH) by inhibiting the activity of PDK1, which converted the metabolism of human hepatocellular carcinoma (HCC) cells to oxidative phosphorylation, leading to an increase in mitochondrial reactive oxygen species ROS (mtROS) and a decrease in mitochondrial membrane potential (MMP), thereby increasing the apoptosis induced by oxaliplatin (OXA). Furthermore, the present study elucidated that the targeting of PDK1 may be a potential strategy for targeting metabolism in the chemotherapy of HCC. In addition, DIC as an ‘old drug’ exhibits novel efficacy, bringing new hope for antitumor therapy.
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September-2020
Volume 57 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Xu H, He Y, Ma J, Zhao Y, Liu Y, Sun L and Su J: Inhibition of pyruvate dehydrogenase kinase‑1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming. Int J Oncol 57: 733-742, 2020
APA
Xu, H., He, Y., Ma, J., Zhao, Y., Liu, Y., Sun, L., & Su, J. (2020). Inhibition of pyruvate dehydrogenase kinase‑1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming. International Journal of Oncology, 57, 733-742. https://doi.org/10.3892/ijo.2020.5098
MLA
Xu, H., He, Y., Ma, J., Zhao, Y., Liu, Y., Sun, L., Su, J."Inhibition of pyruvate dehydrogenase kinase‑1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming". International Journal of Oncology 57.3 (2020): 733-742.
Chicago
Xu, H., He, Y., Ma, J., Zhao, Y., Liu, Y., Sun, L., Su, J."Inhibition of pyruvate dehydrogenase kinase‑1 by dicoumarol enhances the sensitivity of hepatocellular carcinoma cells to oxaliplatin via metabolic reprogramming". International Journal of Oncology 57, no. 3 (2020): 733-742. https://doi.org/10.3892/ijo.2020.5098