Bufalin enhances the anti-proliferative effect of sorafenib on human hepatocellular carcinoma cells through downregulation of ERK

Yang Gao, Hua Xing Li, Li Tao Xu, Peng Wang, Li Yan Xu, Lorenzo Cohen, Pei Ying Yang, Ke Gu, Zhi Qiang Meng

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The purpose of this study was to investigate the effect of bufalin on the anti-proliferative activity of so-rafenib in the human hepatocellular carcinoma (HCC) cell lines PLC/PRF/5 and Hep G-2 and to determine the relevant molecular mechanism. Concurrent treatment with sorafenib and bufalin at a fixed ratio (25:1) for 48 h resulted in synergistic growth inhibition in HCC cell lines as determined by CCK-8 cell viability assays. Exposure of both PLC/PRF/5 and Hep G-2 cells to this combination of sorafenib (6.25 μM) and bufalin (50 nM) resulted in noticeable increases in apoptotic cell death, as evidenced by the disruption of mitochondria, compared to treatment with either agent alone. Although both sorafenib (6.25 μM) and bufalin (250 nM) alone inhibited the phosphorylation of ERK, the reduction in pERK was more pronounced in the cells treated with a combination of bufalin (50 nM) and sorafenib (250 nM). Furthermore, the inhibitory effect of bufalin on pERK was blocked by the PI3kinase inhibitor LY294002, suggesting that the reduction in pERK induced by bufalin might be mediated by AKT in these two HCC cell lines. Taken together, the results of our study suggest that bufalin enhances the anti-cancer effects of sorafenib on PLC/PRF/5 and Hep G-2 by contributing to the downreg-ulation of ERK.

Original languageEnglish
Pages (from-to)1683-1689
Number of pages7
JournalMolecular Biology Reports
Volume39
Issue number2
DOIs
StatePublished - Feb 2012
Externally publishedYes

Keywords

  • Bufalin
  • Hepatocellular carcinoma
  • Sorafenib
  • Synergistic effect

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