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目的:研究N-乙酰半胱氨酸(NAC)对人肺腺癌细胞A549/DDP耐顺铂的逆转作用,探讨其与多药耐药蛋白表达的关系。方法:以MTT法检测不同浓度NAC处理A549/DDP细胞及顺铂联合对A549/DDP细胞的细胞毒性作用,采用RT-PCR检测NAC作用前后A549/DDP细胞MRPmRNA的表达水平。结果:NAC在10、20及50μg/L浓度时其可以增加A549/DDP对顺铂的敏感性,而在NAC浓度为0.1和1μg/L时未见明显的药物逆转作用。NAC在10、20和50μg/L时其作用后的A549/DDP细胞中MRPmRNA的表达水平低于作用前。结论:NAC可以逆转A549/DDP耐药,由于体外实验中缺乏可能让NAC转为谷胱甘肽(GSH)的微环境,其在另一方面可以通过下调MRP1mRNA的表达,从而导致细胞对DDP的敏感性增加。
AIM: To investigate the reversal effect of NAC on cisplatin-resistant human lung adenocarcinoma cell line A549 / DDP and its relationship with multidrug resistance protein expression. Methods: MTT assay was used to examine the cytotoxicity of A549 / DDP cells treated with different concentrations of NAC and cisplatin on A549 / DDP cells. The expression of MRP mRNA in A549 / DDP cells was detected by RT-PCR. Results: NAC could increase the sensitivity of A549 / DDP to cisplatin at concentrations of 10, 20 and 50μg / L, but no significant drug reversal at NAC concentrations of 0.1 and 1μg / L. The expression level of MRP mRNA in A549 / DDP cells treated with NAC at 10, 20 and 50μg / L was lower than that before treatment. CONCLUSIONS: NAC can reverse A549 / DDP resistance. Due to the lack of microenvironment in vitro that may convert NAC to glutathione (GSH), NAC can down-regulate the expression of MRP1 mRNA, Increased sensitivity.