索拉菲尼联合TRAIL对诱导人肝癌细胞SMMC-7721凋亡的影响

Effect of Sorafenib Combined with TRAIL on Proliferation and Apoptosis of Human Hepatocellular Carcinoma Cells SMMC-7721

目的观察索拉菲尼(SOR)联合肿瘤坏死因子相关凋亡诱导配体(TRAIL)对肝癌细胞株SMMC-7721增殖及凋亡的影响。方法培养人肝癌细胞株SMMC-7721,进行同步化,分为对照组(无血清培养基)、SOR不同浓度干预组、TRAIL不同浓度干预组及SOR联合TRAIL组,用噻唑蓝(MTT)比色法检测细胞生长抑制率及流式细胞仪作凋亡分析,Western blot法检测Mcl-1蛋白表达。结果 MTT法结果显示不同浓度SOR或TRAIL单药处理组,其细胞生长抑制率随着浓度的增加而逐渐增强,而SOR(2μmol/L)联合TRAIL组,其抑制率均高于TRAIL不同浓度干预组(P<0.05)。3组药物干预组细胞凋亡率均显著高于对照组(P<0.01),SOR干预组(2μmol/L)的细胞凋亡率与TRAIL干预组(100 ng/ml)比较差异无显著性(P>0.05),而SOR联合TRAIL组(2μmol/L+100 ng/ml)的细胞凋亡率显著高于其他2组(P<0.05)。SOR联合TRAIL可明显抑制SMMC-7721细胞内Mcl-1的表达(P<0.05)。结论SOR联合TRAIL能够抑制肝癌细胞SMMC-7721的增殖,增强其凋亡,其机制可能为通过Mcl-1发挥了协同作用。

Objective To investigate effect of Sorafenib combined with tumor necrosis factor-related apoptosis inducing ligand （TRAIL） on proliferation and apoptosis of hepstocellular carcinoma cells SMMC-7721. Methods Hu- man hepstocellular carcinoma cells SMMC-7721 were cultured in vitro and perforlaed synchronization. The cells were di- vided into control group （serula-free culture media）, Sorafenib intervention group, TRAIL intervention group and Sor- afenib combined with TRAIL intervention group. Cell growth inhibition rate was measured by thiazolyl blue （MTT） asssy method, and apoptosis condition was analyzed by flow cytolaetry, and expression of Mcl-1 protein was detected by western blotting. Results MTT assay showed that growth inhibition fetes in groups by different concentrstions of Sorafenib medi- cation only could increase with increasing concentration, while growth inhibition rate in Sorsfenib （2 μmol/L） combined with TRAIL intervention group was significant higher than that in TRAIL group （P 〈0.05）. Apoptotic fetes in ell three intervention groups were significantly higher than that in control group （P 〈0.01）. but there was no significant difference in apoptosis between Sorsfenib （2 μmol/L） intervention group and TRAIL （ 100 ng/ml） intervention group （P 〉 0. 05） , while apoptofic rste in Sorsfenib combined with TRAIL intervention group （2 μmol/L ＋ 100 ng/lal） was significantly in- creased compared with the other two intervention groups （P 〈0.05）. Sorafenib combined with TRAIL could significantly inhibit Mcl-1 expression in SMMC-7721 cells （P 〈 0.05）. Conclusion Sorafenib combined with TRAIL lasy inhibit proliferation and enhance apoptosis of hepstocellular carcinoma cells SMMC-7721 induced by TRAIL, and its mechanism may play a coordination effect through Mcl-1.