目的：探讨三苯氧胺（TAM）逆转肺癌A549/DDP细胞多药耐药性（MDR）的作用及可能机制。方法以噻唑蓝（MTT）比色法测定TAM对A549/DDP细胞的生长抑制率，流式细胞术检测TAM对A549/DDP细胞内Rho123表达的影响，选取最佳的TAM实验浓度。以MTT法检测TAM对阿霉素（ADM）、吉西他滨（GEM）、顺铂（DDP）的逆转效率，即时聚合酶链反应法检测TAM对A549/DDP细胞多药耐药基因1（MDR1）mRNA水平的变化，蛋白质印迹法检测P糖蛋白（P-gp）表达水平的变化。结果 TAM剂量在10.0μmol/L时对A549/DDP细胞毒性小且可增加细胞内Rho123的蓄积，10.0μmol/L的TAM能增加化疗药物的敏感性，对ADM、GEM、DDP的逆转倍数分别为3.0、7.2、2.0倍，使MDR1 mRNA的表达率较用药前下降35%，并可显著抑制P-gp的表达水平。结论 TAM体外可逆转A549/DDP细胞MDR，提高A549/DDP细胞对化疗药物的敏感性，其机制可能与抑制MDR1表达、减少细胞内药物外排有关。%Objective To explore the reversal effect of Tamoxifen(TAM) on multidrug resistance(MDR) in lung cancer A549/DDP cells and its proposed mechanisms. Methods The growth inhibitory rate of TAM in A549/DDP cells was tested by MTT colorimetry,and the effect of TAM on Rho123 in the A549/DDP cells was detected by flow cytometry,and then,the appro-priate experimental dose of TAM was determined. The MTT colorimetry was employed to detect the reversion efficiency of TAM on the AMD,GEM and DDP,namely,the real-time PCR colorimetry was applied to detect the changes of TAM on the multidrug-re-sistant gene MDR1 mRNA level of A549/DDP cells and the Western blotting assay to test the changes of the expression level of the MDR1 gene product P-gp. Results TAM at the dose of 10μmol/L had little cytotoxicity on A549/DDP cells and could in-crease the storage of Rho123 in the cells,as well as improve the insensitivity of chemotherapeutics,while the reversal multipliers to ADM,GEM and DDP are 3.0,7.2 and 2.0 respectively. The expression rate of MDR1 mRNA was reduced by 35%. It could in-hibit significantly the expression level of MDR1 gene product P-gp. Conclusion TAM can reverse the MDR of A549/DDP cells externally and improve its drug sensitivities,which is probably associated with inhibiting MDR1 gene expression and decreasing the intracellular ADR accumulation.
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