姜黄素联合奥沙利铂对肠癌RKO细胞增殖的抑制和凋亡的诱导

Curcumin combined with oxaliplatin inhibits cell proliferation and induces apoptosis in human colorectal cancer cell line RKO

目的:观察联合姜黄素和奥沙利铂对诱导人肠癌RKO细胞凋亡以及对凋亡相关蛋白表达的影响.方法:姜黄素和奥沙利铂单独及联合作用于RKO细胞,MTT法检测细胞增殖抑制率,流式细胞术检测细胞凋亡,免疫印记检测凋亡相关蛋白的表达.结果:MTT结果表明单药姜黄素作用RKO细胞24、48和72 h的IC50值分别为64.14 mol/L±3.97 mol/L、34.02 mol/L±2.47 mol/L和18.66 mol/L±0.29 mol/L.单药奥沙利铂作用24、48和72 h的IC50值为36.97 g/mL±1.26 g/mL、20.34 g/mL±2.29 g/mL和9.92 g/mL±0.92 g/mL.选用低浓度的药物(20 mol/L的姜黄素和10 g/mL的奥沙利铂)联合处理RKO细胞24 h,结果显示与相应浓度姜黄素、奥沙利铂单药组相比,两药联合组对RKO的增殖抑制率显著增强,细胞凋亡率显著提高(P<0.05).进一步研究发现姜黄素和奥沙利铂联合后,诱导了PARP、caspase3和caspase8活化裂解.结论:姜黄素和奥沙利铂联合用药后,可能通过诱导PARP、caspase3和caspase8裂解,进而抑制肠癌RKO细胞增殖和诱导细胞凋亡.

AIM： To explore whether curcumin and oxalipla- tin have a synergistic effect on cell proliferation and apoptosis in human colorectal cancer cell line RKO. METHODS： RKO cells were treated with cur- cumin and/or oxaliplatin. Cell proliferation was assessed by MTT assay. Cell apoptosis was determined using flow cytometry. Expression of apoptosis-related proteins was detected by Western blot. RESULTS： The IC50of curcumin in RKO ceils at 24, 48 and 72 h after treatment were 64.14 μmol/ L ± 3.97 μmol/L, 34.02 μmol/L ± 2.47μmol/Land 18.66 μmol/L ± 0.29μmol/L, respectively. The IC50 of oxaliplatin at 24, 48 and 72 h were 36.97 μg/mL ± 1.26 μg/mL, 20.34 μg/mL ± 2.29 μg/mL and 9.92 μg/mL ± 0.92 μg/mL, respec- tively. Curcumin （20μmol/L） and oxaliplatin （10 μg/mL） synergistically inhibited cell prolifera- tion and induced cell apoptosis. The expression of cleaved PARP, caspase 3, and caspase 8 was up-regulated after the combination treatment. CONCLUSION： Curcumin combined with ox- aliplatin inhibits cell proliferation and promotes cell apoptosis by regulating apoptosis-related protein expression in human colorectal cancer cell line RKO.