【摘要】 目的 探讨PSC833对骨肉瘤耐药细胞系U2OS/DOX和SaOS/DOX的逆转作用及其机制。方法 用MTT法和细胞计数法测定PSC833逆转MDR的活性;用流式细胞仪观察PSC833对细胞内Rh123积聚和外排的影响;用免疫荧光技术定量检测逆转剂对P-gp表达水平的影响。结果 PSC833对DOX敏感系U2OS和SaOS无明显作用。PSC833能显著增加DOX对U2OS/DOX和SaOS/DOX的细胞毒性作用,逆转效果明显强于VPL和CSA,且存在剂量依赖关系。PSC833能减少耐药细胞系内Rh123的外排,增加Rh123的积聚,而对P-gp的表达水平没有明显影响。结论 PSC833能逆转U2OS/DOX和SaOS/DOX的MDR,其效果明显优于VPL和CSA,逆转机理在于抑制耐药系细胞膜上P-gp的功能,而对P-gp的表达水平没有影响。更多还原

【Abstract】 Objective To investigate the reversal effect and the mechanism of PSC833 on human osteosarcoma cell lines with multidrug resistance, U2OS/DOX and SaOS/DOX. Methods The reversal efficacy of PSC833 IS MEASURED BY mttAND Typan - blue. The effects of PSC833 on Rhl23 uptade and efflux are analyzed by flow cytometer. The effect of PSC833 on - P - gp expression is analyzed quantitatively by immuno - fluorescence. Results PSC833 greatly increases the cellular toxicity of DOX in U2OS/DOX as well as SaOS/DOX,and is more active than VPL and CSA,but not in U2OS and SaOS.Lts efficacy is dose - dependent . PSC833 decreases cellular Rh123 efflux and increases its accumulation, but has no effect on the expression of P - gp. Conclusion PSC833 can potentiate the toxicity of CDO against U2OS/DOX and SaOS/DOX,reverse MDR,and be more active than VPL and CSA. PSC833 may act by blocking the function of P - gp and have no effect on the expression of P - gp.更多还原