中国肿瘤生物治疗杂志2018,Vol.25Issue(3):246-251,6.DOI:10.3872/j.issn.1007-385x.2018.03.006
miRNA通过Mcl-1基因调控HBV阳性肝癌细胞对索拉菲尼的敏感性
miRNA regulating the sensitivity of HBV-positive hepatocellular carcinoma cells to sorafenib by Mcl-1 gene
摘要
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.关键词
乙型肝炎病毒/肝癌/Mcl-1/miRNA/索拉菲尼Key words
HBV/hepatocellular carcinoma/miRNA/sorafenib分类
医药卫生引用本文复制引用
黄锐,伍刚,许健,郑波,黄凌远,赵婵娟,钟振东..miRNA通过Mcl-1基因调控HBV阳性肝癌细胞对索拉菲尼的敏感性[J].中国肿瘤生物治疗杂志,2018,25(3):246-251,6.基金项目
四川省卫生厅资助项目(No.17PJ587).Project supported by the Foundation of Health Department of Sichuan Province (No.17PJ587) (No.17PJ587)