三氟拉嗪逆转人肾癌MDR的研究

The Experimental Studies on the Reverse Multidrug Resistance of the Kidney Cancer with the Trifluoperazine

目的 :探讨钙调蛋白的抑制剂三氟拉嗪是否具有逆转人肾癌的天然多药耐药性的作用。方法 :对经过病理证实的 36例肾透明细胞癌组织采用RT PCR方法检测mdr 1表达水平 ,高表达的为耐药组 ,无或低表达的为敏感组 ,给予阿霉素和三氟拉嗪处理 ,并采用MTT法评价细胞毒作用 ,流式细胞仪检测细胞内ADR浓度聚集。结果 :三氟拉嗪 (TFP)对肿瘤细胞无明显的细胞毒作用 ;但具有逆转肾癌对ADR的耐药 ,并且在耐药的肾癌中 ,效果更明显 (P <0 0 1)。同样三氟拉嗪(TFP)能增加化疗药物细胞内浓度 ,但未存在剂量 效应相关性 ,具有饱和性。结论 :三氟拉嗪能逆转人肾癌MDR ,可以作为肾癌化疗和辅助用药 。

Objective:To illustrate that the trifluoperazine(TFP) which is the calmodulin inhibitor can reverse multidrug resistance(MDR) of the human kidney cancer.Methods:The tissues of 36 cases with kidney cancer were divided into two groups:resistance drug and no resistance drug based on the expression lever of Mdr 1 gene which was analyzed with reverse transcription polymerase chain reaction(RT PCR),and then treated them with adriamycin(ADR)and trifluoperazine(TFP),after that,we examined the cytotoxicity and accumulation by MTT test and the flow cytometry.Results:The TFP was no obvious effect of the cytotoxicity to tumor cell but it can reverse multidrug resistance of the kidney cancer and increase the ADRs cytotoxicity to the tumor cell,expecially in the resistance drug group( P <0.01),whereas it also could increase the density of the ADR in the cell,but no relative of the dosage and the efficacy.Conclusion:The trifluoperazine may used as the supplementary drug in the chemotherapy to the kidney cancer,its low toxin and side effect make it practical and valuable.