The Role Of Bax On Mitofusin-2 Induced Apoptosis In Hepatocellular Carcinoma Cell Lines

Background and Aim:Mitochondrial GTPase mitofusin-2 gene (Mfn2) is a novel gene that suppresses the proliferation of injury mediated vascular smooth muscle cells (VSMCs) remarkably and has potential apoptotic effect by the mitochondrial apoptotic pathway.Methods:Mfn2 gene expression in Hepatocellular carcinoma (HCC) and nearby normatic liver tissues of patients was detected by Western blotting. Adenoviruses (Ad-mfn2) infected HCC cells and adenoviral vector encoding green fluorescent protein (Ad-GFP) as a control. RNAi was performed by shR-mfn2 and shR-bax to repress mfn2 and bax gene transcription in L02 cells. Cytoplasmatic and mitochondrial proteins were extracted form cells infected and examined Bax/Bcl-2 pathway proteins by western blotting. The effects of mfn2 on the cell cycle distribution and apoptosis were measured by flow cytometry analysis.Results:We found that mfn2 was significantly downregulated in HCC tissues compared to nearby normatic tissues. Overexpression of mfn2 results in inhibiting cell proliferation and inducing apoptosis, by increasing the level of the active Caspase-3 and cleavage PARR Overexpression of mfn2 also induced cytochrome c release to cytoplasm by enhancing bax translocation to mitochondrial membrane from cytoplasm. Upregulation of mfn2 also promote the apoptosis of HCC cells but was dramatically suppressed by shR-bax.Conclusions:Our results show that mfn2 gene is a potential tumor suppressor target which could significantly promote apoptosis via Bax and inhibit the proliferation of HCC cells. This gene may be look as an important therapeutic target for the treatment of tumors or hyper-proliferative diseases.