利福霉素逆转多药耐药细胞系A549/ADM的实验研究

    Rifamycin in reversing multidrug-resistance in human lung adenocarcinoma cell line A549/ADM: An experimental study

    • 摘要: 目的: 探讨利福霉素逆转人肺腺癌细胞多药耐药的发生及逆转机制。方法: 采用流式细胞仪检测敏感细胞系、耐药细胞系的P糖蛋白(P-gp)和多药耐药相关蛋白(MRP)表达;MTT法检测其对多种化疗药物的耐药程度及利福霉素对其耐药的逆转效果;采用细胞内阿霉素含量的方法测定利福霉素对多药耐药的逆转作用。结果: 多药耐药细胞系A549/ADM的P-gp、MRP表达分别为74.8%和61.2%;加用利福霉素后,A549/ADM细胞内ADM的含量显著增加,A549/ADM对ADM敏感性增加了2.51倍,对VCR、DDP及VP-16敏感性分别增加7.38倍、1.29倍、2.86倍。结论: A549/ADM对多种常见肿瘤化疗药物表现不同程度耐药,其耐药性可能与P-gp、MRP高表达有关;利福霉素对A549/ADM的多药耐药有一定的逆转作用。

       

      Abstract: Objective: To investigate the mechanisms of multidrug resistance in human lung adenocarcinoma cell line A549/ADM and the reversion of multidrug resistance with rifamycin.Methods: The expressions of P-glycoprotein(P-gp) and multidrug resistance-associated protein(MRP) were detected with flow cytometry.The resistance to chemotherapeutic drugs and the reversion with rifamycin was evaluated with MTT assay.The accumulation of ADM in A549/ADM cells was evaluated with flow cytometry.Results: The expression of P-gp and MRP enhanced significantly(74.8% and 61.2%) compared with A549 cells;with rifamycin(8 μg/ml)added,the sensitivity of A549/ADM cells to ADM raised by 2.51 times and accumulation of ADM in A549/ADM cells was significantly increased.The sensitivity to VCR,DDP and VP-16 increased by 7.38,1.29 and 2.86 times respecitively.Conclusions: A549/ADM cells are resistant to many commonly used anti-cancer chemotherapeutic drugs and the resistance might be related to P-gp and MRP overexpression.Rifamycin could reverse the MDR of lung adenocarcinoma cell lines A549/ADM.

       

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