论文部分内容阅读
研究甲诺孕酮 (NOM )和屈洛昔芬 (DRO)对K5 6 2 /AO2细胞株耐药基因mdrⅠ、谷胱甘肽S 转移酶 (GSTπ)、拓扑异构酶Ⅱα(TopoⅡα)和多药耐药相关蛋白 (MRP)的调节。 方法 应用细胞培养技术 ,采用MTT比色法、免疫组织化学、逆转录 聚合酶连反应和流式细胞术分析。结果 NOM和DRO均可明显提高K5 6 2 /AO2细胞株对阿霉素 (ADM)的敏感性 ,增加细胞内ADM和累量。可显著下调mdrⅠ、GSTπ的mRNA和蛋白表达 ,明显上调TopoⅡα基因表达。K5 6 2敏感株的GSTπ基因表达同样被抑制。都具有明显的时间依赖性。MRP基因表达的变化差异无统计学意义。结论 NOM和DRO可明显逆转K5 6 2 /AO2细胞株对ADM的耐药性。NOM与异搏定逆转强度相似 ;两药对mdrⅠ、GSTπ和TopoⅡα基因表达均有明显调节作用。调节呈时间依赖性。
To investigate the effects of normadropropionate (NOM) and droloxifene (DRO) on the resistance genes mdrⅠ, glutathione S transferase (KSTπ), topoisomerase Ⅱα (TopoⅡα) Regulation of drug resistance associated protein (MRP). Methods The cell culture technique was used to analyze the expression by MTT colorimetric assay, immunohistochemistry, RT-PCR and flow cytometry. Results Both NOM and DRO significantly increased the sensitivity of adriamycin (ADM) to K562 / AO2 cells and increased intracellular ADM and accumulation. The mRNA and protein expressions of mdr Ⅰ and GSTπ were significantly down-regulated, and TopoⅡα gene expression was significantly up-regulated. The GSTπ gene expression of K5 6 2-sensitive strains was similarly inhibited. All have obvious time dependence. There was no significant difference in MRP gene expression. Conclusion NOM and DRO can reverse the drug resistance of K562 / AO2 cells to ADM. NOM and verapamil reverse intensity similar; two drugs on mdr Ⅰ, GSTπ and Topo Ⅱ α gene expression significantly regulation. Regulatory time-dependent.