舒林酸诱导人肝细胞癌凋亡及对环氧合酶-2和Bcl-2蛋白表达的影响

The effects of sulindac on induction of apoptosis and expression of cyclooxygenase-2 and Bcl-2 protein in human hepatocellular carcinoma cells

目的 探讨舒林酸在肝细胞癌化学预防和治疗中的应用价值。方法 采用人肝细胞癌细胞株SMMC772 1、HepG2 作为研究对象。体外药物敏感试验检测不同浓度和作用时间的舒林酸对细胞的增殖抑制效应 ;分别用Hoechst 332 5 8细胞核荧光染色和透射电镜观察舒林酸诱导的细胞凋亡的形态学改变 ,并计算相应的细胞凋亡指数 (AI) ;应用Western斑点印迹法观察不同浓度舒林酸作用后细胞内环氧合酶 2 (COX 2 )和凋亡抑制蛋白Bcl 2表达程度的变化。结果 舒林酸对人肝细胞癌细胞SMMC772 1、HepG2 具有显著的增殖抑制和凋亡诱导作用 ,并且具有时间和剂量依赖性。舒林酸对不同类型细胞的杀伤率和凋亡诱导效应有显著差异。经舒林酸 2mmol/L和 4mmol/L作用 2 4h后 ,细胞内COX 2和Bcl 2蛋白的表达比未经舒林酸作用的细胞表达明显减少。结论 舒林酸在体外对人肝细胞癌细胞株SMMC 772 1和HepG2 具有显著的增殖抑制和诱导凋亡作用 ,且与其抑制细胞内COX 2和Bcl

Objective To investigate the value of sulindac in chemoprevention and treatment of human hepatocellular carcinoma. Methods The hepatocellular carcinoma cell(HCC) lines (SMMC 7721 and HepG 2) were used in this study. Antiproliferation effects was measured by MTT assay, and apoptosis, cyclooxygenase 2 (COX 2) and Bcl 2 were detected by Western dot blotting. Results The growth inhibition and apoptosis of HCC cells could be induced by sulindac in a dose and time dependent manner. The effects of growth inhibition and apoptosis induction were different between 2 cell lines. After 24 hours of incubation with sulindac at the concentration of 2 mmol/L and 4 mmol/L, the expression of COX 2 and Bcl 2 were markedly reduced. Conclusions Sulindac could inhibit the growth of two HCC cell lines effectively in vitro by induction of apoptosis, which were associated with the inhibition of COX 2 and Bcl 2 expression.