Shc3 over-expression inhibits apoptosis of HCC cells and is involved in drug resistance

Abstract

Abstract: Objective To investigate the apoptosis and drug resistance mechanism of Src homolog and collagen homolog 3 (Shc3) in human hepatocellular carcinoma (HCC). Methods Human hepatocellular carcinoma cell lines HCCLM3 and HepG2 with stable Shc3 downregulation and their scramble cell control groups were selected, Huh7 and HepG2 cells with stable Shc3 up-regulation and their pCDH control groups were selected. Protein expression levels of Shc3,MEK,p-MEK,ERK and p-ERK were determined by Western blot analysis. The mRNA level of Shc3 were determined by real-time PCR. Apoptotic experiment was used to observe cell apoptosis. CCK-8 assays were used to observe cell proliferation. Results Shc3 down-regulation and up-regulation cell lines were proved. Compared with scramble cells, Shc3 down-regulation significantly decreased activity of MEK/ERK pathway (P＜0.05), promoted cell apoptosis significantly (P＜0.05). Compared with pCDH cells, Shc3 up-regulation increased cell tolerance to sorafenib (P＜0.05), Moreover, significantly enhanced activity of MEK/ERK pathway (P＜0.05). Conclusions Shc3 may increase the resistance of HCC cells to sorafenib by interfering with apoptosis of HCC cells and activating MEK/ERK pathway. The results of this study provide theoretical basis and laboratory basis for targeting at Shc3 in the treatment of hepatocellular carcinoma.

Key words: human hepatocellular carcinoma, Shc3, cell apoptosis, cell resistance

CLC Number:

R739.41

ZHANG Xin-ran, ZHANG Yi, GAO Hui-er, QIANG Zhao-yan, LI Yong-mei. Shc3 over-expression inhibits apoptosis of HCC cells and is involved in drug resistance[J]. Basic & Clinical Medicine, 2020, 40(4): 473-478.

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