尼美舒利与阿霉素联合应用对肝癌HepG_2细胞增殖及凋亡的影响

目的探讨尼美舒利(n im esu lide,NIM)联合阿霉素(adriamyc in,ADM)对人肝癌细胞株HepG2的增殖抑制及诱导凋亡作用。方法采用MTT比色法检测药物的生长抑制作用,应用金正均法判断两药的相互作用,吖啶橙荧光染色观察细胞的形态学改变,流式细胞仪(flow cytom etry,FCM)检测细胞凋亡率。结果MTT结果显示NIM(25、50、100μmol.L-1)与ADM(0.156,0.313,0.625 mg.L-1)联合应用对人肝癌细胞株HepG2的增殖抑制均有不同程度的协同作用(q>1.15),联合用药组与ADM各单药组相比差异有显著性(P<0.01)。吖啶橙荧光染色可见典型的凋亡形态学特征。FCM检测凋亡显示NIM 100μmol.L-1和ADM2.5 mg.L-1单独及联合应用48 h后DNA直方图上均出现典型的亚二倍体“凋亡峰”,联合用药组凋亡率(19.6%)明显高于各单独用药组(2.48%和10.6%)。结论NIM与ADM联合应用具有协同抑制人肝癌细胞株HepG2细胞增殖与诱导其凋亡作用。

Effect of combined nimesulide and adriamycin on proliferation and apoptosis in hepatocellular carcinoma cell line HepG2

Aim To explore the effect of nimesulide in combination with adriamycin on the proliferation and apoptosis in human hepatocellular carcinoma cell line HepG_2.Method The inhibitory effect of the two drugs on the proliferation of HepG_2 was detected with MTT assay.The Jin′s formula was used to analyze their synergic inhibitory effect.The morphologic changes were observed by acridine orange fluorescence staining.Cell apoptosis was detected by flow cytometry(FCM).Results NIM(25,50,100 μmol·L~(-1))in combination with ADM(0.156,0.313,0.625 mg·L~(-1)) showed different synergic effects on the proliferation of human hepatoma cell line HepG_2(q>1.15).It had marked difference between the combined group and the ADM group alone(P<0.01).After incubation with drugs for 48 h,the cells showed distinctive apoptotic characteristics and the apoptosis rate of the combined group(NIM 100 μmol·L~(-1)+ADM 2.5 mg·L~(-1)) was higher than those of the group treated with NIM 100 μmol·L~(-1) or ADM 2.5 mg·L~(-1) alone(19.6% vs 2.48%,10.6%).Conclusion The combination of selective COX-2 inhibitor NIM and ADM can synergetically suppress the proliferation and enhance apoptosis in human hepatoma cell lines HepG_2.