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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 study the drug resistance mechanism of paclitaxel-resistant cell line A2780 / Taxol, A2780 / (DDP + Taxol) and A2780 / Taxol-1 by different induced drug resistance methods to provide a model for the study of clinical drug resistance in accordance with. Methods: The cells were treated with increasing drug concentration and high dose shock until the cells could stably grow in 2.5μg · ml ~ (-1) paclitaxel. The drug resistance and the inhibitory rate of paclitaxel to each group of cells were determined by MTT assay, and the drug resistance was tested again 3 months after cryopreservation. Results: The IC 50 values of A2780 and A2780 / DDP cells were (0.23 ± 0.04) μg · ml -1 and (0.26 ± 0.02) μg · ml -1 -1). The A2780 / Taxol-1 cell line was established by gradually increasing the concentration of A2780 and the IC 50 of paclitaxel was (6.63 ± 0_31) μg · ml -1 ), Resistance multiple was 28.83. A2780 / Taxol and A2780 / (DDP + Taxol) were respectively established by A2780 and A2780 / DDP with high dose impact method. A2780 / Taxol, A2780 / (DDP + Taxol) ), And found that they were 19.65 and 17.96, respectively. There was no significant difference between the two groups (P> 0.05), but the two drug-resistant cell lines A2780 / Taxol, A2780 / Taxol -1 was statistically significant (P <0.05). Simultaneous detection of A2780 / DDP and A2780 / (DDP + Taxol) on cisplatin IC50 difference was not statistically significant (P> 0.05). Conclusion: The drug-resistant cell lines established by the step-by-step induction method are more resistant and resistant than the drug-resistant cell lines established by the high-dose impact method, suggesting that sufficient dosage should be used in clinical drug use. Paclitaxel and cisplatin no cross-resistance. Paclitaxel based on A2780 / DDP cells to establish dual drug-resistant cell lines, paclitaxel on cell resistance to cisplatin had no effect, can not reverse the cisplatin resistance, so cisplatin-resistant patients with multi-drug significance Large, paclitaxel alone may be better.