miRNA regulating the sensitivity of HBV-positive hepatocellular carcinoma cells to sorafenib by Mcl-1 gene / 中国肿瘤生物治疗杂志

ABSTRACT

@#[Abstract] Objective: To investigate the miRNAs that can intervene Mcl-1 expression in HBV-related liver cancers and to study their synergistic anti-cancer effect with sorafenib. Methods: The expressions of miR-29, miR-101 and miR-193b in HepG2.2.15 (HBV positive) and HepG2.vc (HBV negative) cells were detected by qPCR. miRNA mimics of low expressed genes in HepG2.2.15 cells were synthesized and transfected into HepG2.2.15 and HepG2.vc cells, respectively. qPCR was used to detect target miRNA expression. Western blotting was used to detect the expression of mcl-1 protein in cells before and after transfection.At the same time, (1×10-9)~(1× 10-3) mol/L of sorafenib was add to both transfected and non-transfected HepG2.2.15 and HepG2.vc cells; 72 h later, the IC50 and cell apoptosis was evaluated. Results: The expression of miR-193b in HepG2.2.15 cells was significantly lower than that in HepG2.2.15 cells (P <0.05). The expression of miR-193b in HepG2.2.15 cells and HepG2.2.15 cells was significantly higher after miR-193b mimics transfection (P <0.05). Compared with HepG2.vc cells, the expression of Mcl-1 protein in HepG2.2.15 cells was significantly increased (P <0.05). The expression of Mcl-1 protein in HepG2.2.15 and HepG2.vc cells was significantly decreased after miR-193b mimics transfection (P<0.05). After miR-193b mimics transfection, sorafenib could significantly increase apoptosis rate of both HepG2.2.15 and HepG2.vc cells. Conclusion: The low susceptibility of HBV-related liver cancer to sorafenib may be related with the low expression of miR-193b in cancer cells. Mcl-1 might be used as a target of miR-193b, and miR-193b mimics have a significant synergistic effect with sorafenib.