Overexpression of PINK1 protein on sorafenib induced proliferation and apoptosis inhepatocellular carcinoma HepG2 cells

Backgound & Aims Previous studies have shown that mitochondrial regulation was involved in the development of hepatocellular carcinoma (HCC) cells, but the detail mechanism was complex and unclear. This study investigated the effect of overexpression of mitochondrial protein PINK1 on sorafenib induced proliferation and apoptosis in hepatoma HepG2 cells. Methods First, lentiviruses were used to transfect PINK1 cDNA into vehicle HepG2 cells, named OE‐Pink1‐HepG2, which was of stable expression of PINK1 gene characterized by real‐time fluorescence quantitative PCR and western blot. OE‐Pink1‐HepG2, vehicle transfected HepG2 (NC‐HepG2) as well as parental HepG2 cells were then sub‐cultured and randomly used in designed protocols. In the present or absent of sorafenib, cell proliferation in these cells were determined by CCK8 assay, cell apoptosis was detected by flow cytometry. Western blot was used to detect the expression of PINK1, caspase3, Bcl‐2 and other proteins in each group. Results Compared with vehicle control, the PINK1 mRNA and protein levels were significantly increased in OE‐Pink1‐HepG2 cells (p < 0.05). In basal conation, sorafenib with 10μM was found to induce a cellular inhibition in parental HepG2 cells. While overexpression of PINK1, it was found to cause a significant higher proliferation inhibitory rate in OE‐Pink1‐HepG2 than that in NC‐HepG2 cells (p < 0.05). Consistent enhanced apoptotic rates by PINK1 gene were substantially obtained. Moreover, the overexpression of PINK1 could promote sorafenib induced‐ cleavage of caspase‐3 and decrement of bcl‐2, and further promote cell death in those cells. Conclusions Taken together, our preliminary data suggested that the enhancement of PINK1 gene may promote the sensitivity of HCC cells to sorafenib, which might provide potential therapeutic strategy for the treatment of HCC in the future.