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目的 动态观察阿霉素(ADM)诱导肝癌细胞SMMC-7721耐药性的产生，了解多药耐药相关蛋白(MRP)在其耐药机理中的作用。方法 分别用逐步提高培养基中ADM的浓度诱导SMMC-7721细胞和用含不同ADM浓度的培养基直接短期培养SMMC-7721细胞的方法，诱导细胞产生耐药性，绘制剂量反应曲线，确定细胞耐药倍数，RT-PCR法测定细胞MRP mRNA的表达水平，流式细胞仪检测细胞内柔红霉素(DNR)的浓度。结果 随着培养基中ADM浓度的逐步提高，MRP mRNA的表达也逐渐增强，细胞内DNR浓度明显下降，SMMC-7721细胞的耐药性逐渐增加；用含不同ADM浓度的培养基直接培养亲代细胞后，虽然MRP mRNA表达明显升高，但细胞内DNR浓度仍维持较高水平，并且绝大部分细胞短期内死亡。结论 ADM可以逐步诱导肝癌细胞产生耐药性，其机理主要是由于MRP基因过度表达，其蛋白产物能明显降低细胞内化疗药物浓度，从而细胞获得耐药性。“,”Objective To dynamically study the formation of multidrug resistance(MDR) of human hepatocellular carcinoma cell SMMC-7721 induced by Adriamycin (ADM) and the role of multidrug resistance-associated protein(MRP) in its mechanisms.Methods Hepatocellular carcinoma cell SMMC-7721 was cultured in RPMI-1640 medium containing ADM with progressively increased concentration or directly cultured in medium containing different concentrations of ADM. Resistant index of drug-resistant variants of SMMC-7721 cell was determined by drawing cell dosage-reaction curves.Levels of MRP mRNA expression were detected by reverse transcription-polymerase chain reaction(RT-PCR). Intracellular rubidomycin(DNR) concentration was examined by flow cytometry(FCM).Results With progressive increasing of ADM concentration in medium resistant index and levels of MRP mRNA expression were correspondingly increased but intracellular DNR concentration was markly reduced. When parental cells were directly cultured in medium containing different concentrations of ADM, the higher the ADM concentration, the higher the level of MRP mRNA expression, but intracellular DNR concentration was kept at the similar high level and most cells died. Conclusion ADM may progressively induce SMMC-7721 cell resistant to multiple chemotherapeutic drugs with reduced intracellular DNR accumulation associated with the overexpression of MRP gene.