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目的:观察藤黄酸(gambogicacids,GA)对肝癌细胞凋亡的诱导作用并探讨其分子作用机制。方法与结果: 采用MTT比色法检测藤黄酸对人肝癌和人正常肝细胞增殖作用的影响,结果表明,藤黄酸对人肝细胞性肝癌SMMC 7721 细胞株和QGY 7701细胞株有明显增殖抑制作用,并呈剂量依赖性,而对正常人肝组织L 02细胞株作用相对较弱;光镜及电镜形态学观察结果显示,给予GA后,肝癌细胞发生明显的细胞凋亡形态学变化,如细胞体积变小,细胞核固缩,出现凋亡小体等;采用RT PCR和Westernblotting方法检测baxmRNA以及bax和p53蛋白表达变化,结果表明GA可诱导baxmR NA及bax和p53蛋白表达上调;琼脂糖凝胶电泳显示,给予GA后,SMMC-7721裸小鼠移植瘤组织呈现典型的DNAladder 电泳梯状条带。结论:藤黄酸可显著抑制人肝癌细胞的增殖,其分子作用机制可能通过促进bax和p53表达上调,从而诱导人肝细胞性肝癌细胞凋亡。
Objective: To observe the induction effect of gambogic acid (GA) on hepatoma cell apoptosis and to explore its molecular mechanism. Methods and Results: The effects of gambogic acid on proliferation of human hepatocellular carcinoma (HCC) and human normal hepatocytes were detected by MTT assay. The results showed that gambogic acid significantly enhanced the proliferation of human hepatocellular carcinoma SMMC 7721 and QGY 7701 cells Inhibition, and in a dose-dependent manner, while the normal human liver L 02 cell line is relatively weak; light microscopy and electron microscopy morphological observation showed that after the administration of GA, significant morphological changes of hepatocellular carcinoma cells apoptosis, Such as smaller cell size, pyknotic nuclei, apoptotic bodies, etc .; RT-PCR and Western blotting were used to detect the expression of bax and p53, bax and p53. The results showed that GA could up-regulate the expression of baxmR NA, bax and p53, Gel electrophoresis showed that, after administration of GA, SMMC-7721 nude mice transplantation tumor tissue showed a typical DNAladder electrophoresis ladder strip. CONCLUSION: Gambogic acid can significantly inhibit the proliferation of human hepatocellular carcinoma cells, and its molecular mechanism may induce the apoptosis of human hepatocellular carcinoma cells by up-regulating the expression of bax and p53.