紫杉醇与常规化疗药物对人骨肉瘤细胞的毒性比较

A comparison study between the cytotoxity of paclitaxel and that of three traditional chemotherapeutic drugs against human osteosarcoma cells

目的:比较紫杉醇与阿霉素、甲氨蝶呤及顺铂对人骨肉瘤细胞的毒性作用强度及多药耐药特性,并研究其相互作用。方法:应用细胞计数、形态学观察、AO/EB染色、流式细胞术等方法比较紫杉醇与上述3种常规化疗药物对MG-63、新鲜骨肉瘤组织块及荷瘤裸鼠的作用;原位杂交及western blot研究紫杉醇和阿霉素分别诱导的MG-63多药耐药细胞模型中MDR-1的表达;比较维拉帕米逆转其耐药倍数。结果:紫杉醇与常规化疗药物有一定协同作用,单独应用时对人骨肉瘤细胞的抑制率稍低于其他3种药物,但诱导的凋亡率最高;紫杉醇与阿霉素诱导的多药耐药对MDR-1的依赖程度不同。结论:紫杉醇与阿霉素、甲氨蝶呤及顺铂对骨肉瘤细胞有协同作用,且对耐阿霉素的骨肉瘤细胞有杀伤作用。

Objective To compare the cytotoxity of paclitaxel with that of three traditional chemotherapeutic drugs against human osteoasarcoma cells. Methods The effects of paclitaxel, adriamycin, methotrexate and cisplatinon on human osteosarcoma cell line MG-63, fresh osteosarcoma specimens and nude mice with osteosarcoma were assessed by MTF test, morphologic observation and flow cytometry. The expression of MDR-1 in multi-drug resistant MG-63 cell models induced separately by paclitaxel and adriamycin was detected by in situ hybridization and western blot. Results Synergistic cytotoxicity existed in paclitaxel and the three chemotherapeutic agents. Although inhibition ratio of paclitaxel to the cells was lower than that of adriamycin, mathotrexate or cisplatin, the apoptosis ratio induced by paclitaxel was higher than those of the three agents. The MDR-1-dependence extent was different in MDR induced by paclitaxel and adriamycin. Conclusion Paclitaxel may have a synergistic effect on osteosarcoma cells with adriamycin, methotrexate and cisplatinon, and have a curative effect on adriamycin-resistant osteosarcoma cases.