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目的:以白血病多药耐药细胞系K562/A02为对象,验证苦参碱能否逆转其对柔红霉素的耐药性。方法和结果:经MTT法发现苦参碱50mg/L能增加K562/A02对柔红霉素的敏感性,使柔红霉素半数抑制浓度(IC50)由1492mg/L降至829mg/L,部分逆转了K562/A02对柔红霉素耐药性,逆转倍数为180倍。经流式细胞仪,免疫组化、逆转录—多酶链式反应证明苦参碱逆转K562/A02耐药性机制主要为:苦参碱降低多药耐药基因mdr-1的mRNA表达,使细胞膜上P-170糖蛋白量减少,从而降低经P-170糖蛋白介导的细胞内柔红霉素外排能力,细胞内柔红霉素浓度升高,增强了K562/A02对柔红霉素敏感性。而苦参碱对K562/s敏感细胞系无上述作用
Objective: To verify whether matrine can reverse its resistance to daunorubicin in a multidrug-resistant leukemia cell line K562/A02. METHODS AND RESULTS: MTT assay showed that matrine 50 mg/L increased the sensitivity of K562/A02 to daunorubicin, reducing the half-inhibitory concentration (IC50) of daunorubicin from 14 to 92 mg/L to 8 to 29 mg. /L partially reversed K562/A02 resistance to daunorubicin, with a reversal multiple of 180. By flow cytometry, immunohistochemistry, reverse transcription-multiplexase chain reaction demonstrated that the matrine reversal mechanism of K562/A02 drug resistance is mainly: matrine reduces multidrug resistance gene mdr-1 mRNA expression, so that The amount of P-170 glycoprotein on the cell membrane is reduced, thereby reducing intracellular daunorubicin efflux ability mediated by P-170 glycoprotein, increasing the intracellular concentration of daunorubicin, and enhancing K562/A02 against rhodoerythrin Susceptibility. Matrine does not have the above effect on K562/s sensitive cell lines