摘要
目的:探讨托瑞米芬(TOR)与表阿霉素(EADM)联用对人肺癌细胞株A549、H1299细胞生长与凋亡的影响及其机制。方法:用MTT比色法检测TOR的化疗增敏作用,用流式细胞仪检测细胞周期的变化及p-gp在两种肺癌细胞中的表达。结果:TOR(≥20μmol/L)能直接抑制两种细胞的生长,低剂量的TOR(5、10μmol/L)与EADM联用后的抑制率均低于单用EADM组(P<0.01),并呈现浓度依赖性。两者联用可引起两种肿瘤细胞凋亡,呈现浓度依赖性。两种细胞周期均发生明显变化。13.1%A549细胞有p-gp的存在,44.9%H1299细胞有p-gp的存在。结论:低浓度的托瑞米芬与表阿霉素联用对两种细胞有明显的协同作用。A549细胞的TOR对EADM的协同作用较H1299细胞强。其化疗增敏效应可能与增加肿瘤细胞凋亡、改变细胞周期分布有关。P53基因可能参与了TOR对两种细胞的化疗增敏及逆转耐药的调节。
Objective： To study the effects of toremifene combined with epirubicin on human lung cancer cell lines A549 （ p53 - positive）, H1299 （ p53 - negative） and its mechanisms. Methods ： The cytotoxic of effects of these agents on the two cell lines was evaluated by MTT assay. Distribution of cell cycle and rate of apoptosis and the expression of p-gp in the two cell lines were determined by flow cytometry. Results：Toremifene（≥20μmol/L） could inhibit the growth of the two cells directly. The IR（ inhibitory rate） of the low dose toremifene（5,10μmol/L） combined with anti - tumor drugs were higher than that of anti - tumor drugs alone. The inhibitory rate of the cell lines also increased with increases in the agents concentration. Toremifene and its combination with epirubicin could induce two cell lines apoptosis markedly. The ratio of apoptosis would increase with increases in the concentration of toremifene. Toremifene combined with epirubicin could couse the two cells cycle to change . The expression level of p - gp of H1299 cells（44.9% ）was higher than that of A549 cells（ 13.1% ）. Conclusion： The low dose toremifene combined with epirubicin show significant synergistic anti - tumor effects on the two cell lines. Toremifene combined with epirubicin could induce the two cell lines apoptosis markedly. The synergistic anti - tumor effects on A549 cells was higher then that on H1299 cells. The expression level of p - gp of H1299 cells was higher than that of A549 cells. The mechanism of effects could be related with change of phase in cell cycles and apoptosis, which may involve a p53 gene dependent pathway.
出处
《现代肿瘤医学》
CAS
2007年第4期498-501,共4页
Journal of Modern Oncology
