不同方法建立卵巢癌紫杉醇耐药细胞株对临床用药方案的启发  

Illumination from Establishing Drug Resistant Ovarian Cancer Cell Lines on the Found of the Sensitive Ovarian Cancer Cell Lines A2780 and A2780/DDP with Different Methods

作　　者：黄在菊[1] 杨守华[1] 李敏[1] 王泽华[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院妇产科教研室,武汉430022

出　　处：《中国药师》2008年第10期1135-1137,共3页China Pharmacist

基　　金：国家自然科学基金资助项目(NO.30070786)

摘　　要：目的:用不同的诱导耐药方法培养紫杉醇耐药细胞株A2780/Taxol,A2780/(DDP+Taxol),A2780/Taxol-1,以进一步探讨卵巢癌耐药机理,为临床逆转耐药研究提供模型依据。方法:采用逐步增加药物浓度和大剂量冲击两种方法处理细胞,直至细胞能在2.5μg·ml^(-1)紫杉醇中稳定生长。用四甲基偶氮唑蓝(MTT)法测定其耐药性及紫杉醇对各组细胞的抑制率,并在冻存3个月后再次检测耐药性。结果:MTT法检测A2780,A2780/DDP细胞对紫杉醇的药物半数抑制浓度(IC_(50))分别为(0.23±0.04)μg·ml^(-1)和(0.26±0.02)μg·ml^(-1),采用逐步增加药物浓度诱导法历经九个月时间建立A2780的紫杉醇耐药细胞株A2780/Taxol-1,对紫杉醇的IC_(50)为(6.63±0_31)μg·ml^(-1),耐药倍数为28.83。采用大剂量冲击法以A2780和A2780/DDP为对象建立各自的紫杉醇耐药细胞株A2780/Taxol、A2780/(DDP+Taxol),检测大剂量冲击法建立的A2780/Taxol,A2780/(DDP+Taxol)耐药性,发现它们对紫杉醇的耐药倍数分别为19.65,17.96,两者比较无统计学差异(P>0.05),而两种方法建立的紫杉醇耐药细胞株A2780/Taxol、A2780/ Taxol-1的耐药性有统计学差异(P<0.05)。同时检测A2780/DDP和A2780/(DDP+Taxol)对顺铂的IC50差异无统计学意义(P>0.05)。结论:通过逐步诱导法建立的耐药细胞株比通过大剂量冲击法建立的耐药细胞株耐药性稳定,耐药性显著增高,提示临床用药中应足剂量用药。紫杉醇与顺铂无交叉耐药。在A2780/DDP细胞基础上使用紫杉醇建立双耐药细胞株时,紫杉醇对细胞的顺铂耐药性无影响,不能逆转其顺铂耐药性,所以对顺铂耐药患者多药合用意义不大,单用紫杉醇可能为佳。Objective：To culture the drug resistant cell lines A2780/Taxol and A2780/（DDP＋Taxol）,A2780/Taxol-1 on the found of the sensitive ovarian cancer cell lines A2780 and A2780/DDP for the use of searching for the new drug resistant mechanism and clinical therapeutic methods. Method：Two kinds of methods were used in the experiment,, increasing the concentration of Taxol step by step, one was results, another was always using the highest concentration to treat with the cells, the cells were cultured in a much higher concentration as far as they were resistant to one kind of concentration, the drug resistant ability to Taxol was Measured by MTT assay and once again after the cells were frozen for three months, then the differnces was compared between two groups. Result：The IC50 value of A2780 and A2780/DDP were （0.23±0.04）μg·ml^-1,（0.26±0.02）μg·ml^-1 respectively, the cells were called that had been induced for 9 months by using the first method A2780/Taxol^-1. It＇s IC50 was（6.63±0.31）μg·ml^-1 and resistant factor was 28.83 multiple. The cells A2780/Taxol,A2780/（DDP＋Taxol） were acquired by using the second method. Their IC50 value and resistant factor were 19.65 and 17.96. all the results were compared, we found the difference between the cells A2780/Taxol-1 and A2780/Taxol was significant （P〈0.05）, whereas that in the cells A2780/Taxol and A2780/（DDP＋Taxol） had no significant difference （P〉0.05）. the resistance to cisplatin in A2780/DDP and A2780/（DDP＋Taxol） cells were also inspected and found there had not significant difference between them （P〉0.05）.Conclusion：Both the two methods could establish the drug resistant cell lines, the resistant ability of cells induced by using the first method was more higher than the second, maybe there had different mechanisms in the process of producing drug resistance, but the second was much more according with the clinical model, and the result also suggest using the single taxol to the patient may be much bet

关 键 词：肿瘤 卵巢 耐药 紫杉醇 

分 类 号：R737.31[医药卫生—肿瘤]