Abstract: 【Abstract】〓Objective〓To explore the effect and mechanism of lupeol on proliferation and apoptosis of hepatocellular carcinoma SMMC-7721 cells. Methods〓The effect of lupeol on growth inhibition of hepatocellular carcinoma SMMC-7721 cells and normal liver cells L-02 were analyzed by MTT assay. Cell apoptosis were measured and analyzed by flow cytometry and caspase enzymatic assays, and the expressions of TRAIL receptor and anti-apoptotic proteins were determined by Western blot. Results〓The proliferation of SMMC-7721 cells were dramatically inhibited by lupeol (IC50=40 μmol/L), with almost no toxicity to normal cells L-02. The apoptotic rates of SMMC-7721 cells were 5.5%, 12.6%, and 28% treated with lupeol for 48 hours at concentration distribution 30, 40, and 50 μmol/L. The expressions of anti-apoptotic pretein c-FLIPL was down-regulated and the activities of caspase-8 and -3 were increased in a concentration-dependent manner. Conclusion〓Lupeol induces apoptosis of hepatocellular carcinoma cells through down-regulation of c-FLIPL and activation of caspase-dependent pathways, consequently inhibiting proliferation of cells.

Key words: Lupeol, Hepatocellular carcinoma, Apoptosis, c-FLIPL

摘要： 【摘要】〓目的〓探讨羽扁豆醇(lupeol)对人肝癌SMMC-7721细胞生长和凋亡的作用及机制。方法〓采用MTT法检测lupeol对肝癌细胞 SMMC-7721和正常肝细胞L-02的增殖抑制作用,流式细胞法检测细胞凋亡情况,Western blot检测TRAIL受体及抗凋亡蛋白表达变化,比色法分析caspase-8、-9、-3酶活性改变。结果〓lupeol对SMMC-7721细胞具有明显的增殖抑制作用(IC50=40 μmol/L),而对正常肝细胞L-02无细胞毒作用;lupeol在30、40、50 μmol/L浓度范围诱导SMMC-7721细胞48小时的凋亡率分别为5.5%、12.6%、28%;抗凋亡蛋白c-FLIPL表达下调,caspase-8及caspase-3活性增强均呈剂量依赖性。结论〓Lupeol通过下调c-FLIPL表达激活caspase通路诱导肝癌细胞凋亡,对肝癌细胞增殖发挥抑制作用。

关键词: 羽扁豆醇, 肝癌细胞, 凋亡, c-FLIPL