维生素E琥珀酸酯体外防护顺铂肝细胞毒性并增强其抗肿瘤细胞增殖活性

Vitamin E succinate ester prevents from cytotoxicity of cisplatin in hepatocytes and enhances its antiproliferative activities

目的 研究维生素E琥珀酸酯 (VES)对顺铂(CP)肝细胞毒性及联合用药增强抗肿瘤活性的可能。方法 用二步灌流法分离人和大鼠肝细胞 ,接种于胶原铺被的 96孔板 ,细胞贴壁后 ,分别加入一系列浓度的CP ,VES及CP +VES ,于 4 8h用噻唑蓝(MTT)比色法检测细胞存活率 ,并计算半数抑制浓度 (IC50 ) ;同样方法用于检测CP ,VES及CP +VES对人前列腺癌细胞系DU 14 5和人大肠癌细胞系CCL2 2 9的抗增殖作用。结果 CP ,VES ,CP +VES 1mg·L- 1,CP +VES 5mg·L- 1,CP +VES 10mg·L- 1对人肝细胞的IC50 分别为 2 .35 ,>10 0 ,2 .2 6 ,4 .2 5 ,6 .93mg·L- 1;CP ,VES ,CP +VES 5mg·L- 1,CP +VES 10mg·L- 1,CP +VES 2 5mg·L- 1对大鼠肝细胞的IC50 分别为 4 .70 ,>10 0 ,10 .94 ,17.5 7,2 3.2 4mg·L- 1;CP ,VES ,CP +VES 5mg·L- 1,CP +VES 10mg·L- 1,CP +VES 2 5mg·L- 1对DU 14 5和CCL2 2 9的IC50 分别为6 .36 ,5 5 .36 ,5 .0 4 ,4 .85 ,0 .5 8和 9.5 8,39.4 7,7.2 9,4 .2 2 ,2 .4 3mg·L- 1。结论 VES能明显减低CP所致人和大鼠肝细胞毒性 ,增强CP对DU 14 5和CCL2 2

AIM To investigate the effects of vitamin E succinate ester(VES)on cytotoxicity of cisplatin (CP) and to explore the possibility of enhancing antitumor activity by the combination of VES and CP. METHODS Hepatocytes isolated from rats and humans by two step perfusions were used to evaluate cytotoxicity of CP and antiproliferative activity of CP in human prostate cancer cell line DU 145 and human colon cancer cell line CCL229; MTT assays were performed to evaluate cell viabilities. RESULTS Concentration of CP which inhibited 50% cell growth(IC50) was 2.35 and 4.70 mg·L-1 in primary cultures of human and rat hepatocytes, respectively. VES increased IC50 of CP to 6.93 mg·L-1 and more than 100 mg·L-1, respectively; IC50 of CP in DU 145 and CCL229 were 6.36 mg·L-1 and 9.58 mg·L-1, respectively. VES decreased IC50 to 0.58 mg·L-1 and 2.43 mg·L-1, respectively. CONCLUSION VES can decrease CP induced cytotoxicity in human and rat hepatocytes, and enhance antiproliferative activity of cisplatin in DU 145 and CCL229.