表皮生长因子受体抑制剂增敏奈达铂的细胞杀伤作用及机制

Sensibilization of cell-killing effect of nedaplatin by epidermal growth factor receptor inhibitor and the mechanism

目的:探讨表皮生长因子受体(EGFR)特异性抑制剂西妥昔单抗(C225)以及与化疗药物奈达铂(NDP)联合应用对宫颈癌He La细胞的杀伤作用,并分析其作用机制。方法:培养宫颈癌He La细胞;实验分为C225单药组(10、20、40、60、80和160 mg/L)、NDP单药组(1、5、10、20、40和60 mg/L)、C225+NDP联合用药组(C225 40 mg/L分别联合NDP各浓度),每个浓度作用He La细胞后分别培养24、48和72 h后采用MTT法检测细胞抑制率;采用流式细胞术检测细胞凋亡和周期。结果:C225单药不能明显抑制He La细胞增殖;NDP单药对hela细胞有明显抑制作用,C225联合NDP的细胞抑制率明显高于对应的C225或NDP单药(P<0.05)。NDP和C225单独应用均有促进细胞凋亡的作用,联合用药后凋亡率均大于对应的NDP或C225单药(P均<0.05)。NDP或C225单药时,G0-G1期细胞百分比较对照组增加,S期较对照组减少,两药联合后,G0-G1期细胞百分比明显增加(P<0.05),S期细胞百分比明显降低(P<0.05),细胞增殖指数(PI)也逐渐降低(P<0.05)。结论:C225可增强hela细胞对NDP的敏感性,增加细胞凋亡率,G0-G1期阻滞作用增强。

Objective： To explore the cell- killing effect of joint application of epidermal growth factor receptor inhibitor─cetuximab（ C225） and chemotherapeutic drug─nedaplatin（ NDP） on cervical cancer He La cells,analyze the mechanism. Methods： Cervical cancer He La cells were cultured and divided into C225 group（ 10,20,40,60,80 and 160 mg / L）,NDP group（ 1,5,10,20,40 and60 mg / L） and drug combination group（ C225 40 mg / L combined with NDP of different concentrations）; cervical cancer He La cells were treated with C225 and NDP of different concentrations and cultured for 24,48 and 72 hours,respectively; MTT assay was used to detect the apoptotic rate; flow cytometry was used to detect cell apoptosis and cycle. Results： C225 could not inhibit proliferation of cervical cancer He La cells significantly; NDP could inhibit proliferation of cervical cancer He La cells significantly; the cell inhibiting rate of C225 combined with NDP was significantly higher than those of simple C225 and simple NDP（ P〈0. 05）. NDP and C225 used separately could promote cell apoptosis,the apoptotic rate of drug combination of NDP and C225 was statistically significantly higher than that of single NDP and single C225（ P〈0. 05）. The proportions of He La cells of stage G0 and stage G1 in NDP group and C225 group were higher than those in control group,the proportions of He La cells of stage S in NDP group and C225 group were lower than that in control group,the proportions of He La cells of stage G0 and stage G1 in drug combination group increased significantly（ P〈0. 05）,while the proportion of He La cells of stage S decreased significantly（ P〈0. 05）,the proliferation index decreased gradually（ P〈0. 05）. Conclusion： C225 can strengthen the sensitivity of He La cells to NDP,increase cell apoptotic rate and enhance retardation of stages G0 and G1.