Phosphorylation of Bcl-2 plays an important role in glycochenodeoxycholate-induced survival and chemoresistance in HCC

  • Authors:
    • Maojun Zhou
    • Qi Zhang
    • Jinfeng Zhao
    • Mingmei Liao
    • Sailan Wen
    • Manyi Yang
  • View Affiliations

  • Published online on: July 18, 2017     https://doi.org/10.3892/or.2017.5830
  • Pages: 1742-1750
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Abstract

Hepatocellular carcinoma (HCC) is a highly malignant tumor and can evolve rapidly to resistance to chemotherapies. Glycochenodeoxycholate (GCDA), which is toxic and hydrophobic, is the main ingredient in the bile and associated with carcinogenesis of gastrointenstinal tumors. Bcl-2 is the most important anti-apoptotic protein and overexpressed in various human tumors. In the present study, we found that GCDA can induce the chemoresistance of human liver cancer cells and specific depletion of Bcl-2 by RNA interference blocks GCDA-stimulated chemoresistance, which indicate the pivotal role of Bcl-2 in such process. Mechanistically, GCDA simultaneously stimulates phosphorylation of Bcl-2 at Ser70 site and activates extracellular signal-regulated kinase 1/2 (ERK1/2), and inhibition of ERK1/2 by PD98059 (MAPK/ERK1/2 inhibitor) or siRNA (targeting ERK1/2) suppresses GCDA-stimulated phosphorylation of Bcl-2 and significantly attenuates the survival and chemoresistance induced by GCDA in liver cancer cells. Thus, GCDA-induced survival and chemoresistance of liver cancer cells may occur through activation of Bcl-2 by phosphorylation at Ser70 site through MAPK/ERK1/2 pathway, which may contribute to the development of human liver cancer and chemoresistance.
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September-2017
Volume 38 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhou M, Zhang Q, Zhao J, Liao M, Wen S and Yang M: Phosphorylation of Bcl-2 plays an important role in glycochenodeoxycholate-induced survival and chemoresistance in HCC. Oncol Rep 38: 1742-1750, 2017
APA
Zhou, M., Zhang, Q., Zhao, J., Liao, M., Wen, S., & Yang, M. (2017). Phosphorylation of Bcl-2 plays an important role in glycochenodeoxycholate-induced survival and chemoresistance in HCC. Oncology Reports, 38, 1742-1750. https://doi.org/10.3892/or.2017.5830
MLA
Zhou, M., Zhang, Q., Zhao, J., Liao, M., Wen, S., Yang, M."Phosphorylation of Bcl-2 plays an important role in glycochenodeoxycholate-induced survival and chemoresistance in HCC". Oncology Reports 38.3 (2017): 1742-1750.
Chicago
Zhou, M., Zhang, Q., Zhao, J., Liao, M., Wen, S., Yang, M."Phosphorylation of Bcl-2 plays an important role in glycochenodeoxycholate-induced survival and chemoresistance in HCC". Oncology Reports 38, no. 3 (2017): 1742-1750. https://doi.org/10.3892/or.2017.5830