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目的：为了建立人膀胱癌耐阿霉素细胞系并研究它们的生物学特性及药物耐受性的机理。方法：采用人膀胱癌细胞系EJ，经递增阿霉素剂量的方法，历时1年，建立一株耐药亚株EJ／DOR，对其生物学特性及耐药机理进行了研究，并应用反转录PCR检测了MDR1、MRP和DNA TopoⅡ基因的表达。结果：EJ／DOR对阿霉素的相对耐受度较亲本细胞提高了14．3倍；对蒽环类、长春花属生物碱及DNA TopoⅡ靶制剂足叶乙甙有明显的交叉耐药性，但对顺铂、丝裂霉素无明显的交叉耐受性；耐药细胞对柔红霉素的细胞内聚集量显著减少；EJ／DOR并不表达MDR1基因，而MRP基因过表达，但细胞内DNA TopoⅡ基因表达低于亲本细胞。结论：细胞内DNA TopoⅡ基因表达下降及MRP基因过表达是EJ／DOR表现为多药耐受性亚型的主要原因，这种非P－gp介导的非经典型多药耐受性细胞为寻求包括阿霉素在内的化疗方案提供了良好的实验模型。
OBJECTIVE: To establish a human bladder cancer resistant doxorubicin cell line and to study their biological characteristics and drug resistance mechanism. Methods: Human bladder cancer cell line EJ was used to increase the dose of doxorubicin. The drug-resistant sub-strain EJ / DOR was established for one year and its biological characteristics and drug resistance mechanism were studied. Transcriptional PCR was used to detect the expression of MDR1, MRP and DNA TopoII genes. Results: The relative resistance of EJ / DOR to doxorubicin was 14.3 times higher than that of parental cells. There was a significant cross-resistance to anthracycline, vinca alkaloid and DNA TopoⅡ target agent etoposide , But no significant cross-resistance to cisplatin and mitomycin; drug-resistant cells significantly decreased the intracellular accumulation of daunorubicin; EJ / DOR did not express MDR1 gene, but MRP gene was overexpressed The intracellular DNA TopoII gene expression is lower than the parental cells. Conclusion: The decrease of intracellular DNA TopoⅡ gene expression and MRP gene overexpression are the main reasons for EJ / DOR expression in multidrug resistant subtypes. The non-P-gp-mediated multi-drug resistant cells are Seeking a chemotherapy protocol that includes doxorubicin provides a good experimental model.