粉防己碱逆转骨肉瘤细胞系多药耐药性的研究

目的：探讨粉防己碱对骨肉瘤耐药细胞系U20S／DOX的逆转作用及其机制。方法：用MTT法测定粉防己碱逆转多药耐药性的活性；用流式细胞仪检测粉防己碱对染料Rh123在细胞内积聚和外排的水平；用免疫荧光技术，定量检测逆转剂对P糖蛋白表达水平的影响。结果：粉防己碱能显著增加阿霉素对耐药系U2OS／DOX的细胞毒性作用，逆转效果明显强于维拉帕米和环孢霉素A，且存在剂量依赖性。对敏感系U2OS则无明显作用；粉防己碱能使耐药系细胞内Rh123外排减少、积聚增加，而对P-gp的表达水平没有明显影响。结论：粉防己碱能逆转骨肉瘤细胞系的多药耐药性，其效果明显优于维拉帕米和环孢霉素A，逆转的机理在于抑制耐药系细胞膜上P糖蛋白的功能，而对其表达水平没有影响。

Reversion of Multi-Drug Resistance by Tetrandrine in Osteosarcoma Cells

Objective:To investigate the reversal effect and the mechan is m of tetrandrine(TTD)on human osteosarcoma cell lines with multidrug resistance( U_2OS/DOX).Methods:The reversal efficacy of TTD was measured by MTT.The effect of TTD on Rh123 uptake and efflux were analyzed by flow cytometer.The effects of TTD on P-gp expression were analyzed quantitatively by immoluno-fluorescence technique.Results:TTD increased the toxicity of doxorubicin(DOX)in U_2OS/DOX g reatly,and was more active than verapamil(VPL)and cyclosporin A(CSA),but not in U_2OS.Its efficacy was dose-dependent.TTD decreased cellular rhodamine 123(Rh1 23)efflux and increase its accumulation,but had no effect on the expression of P-gp.Conclusion:TTD can potentiate the toxicity of DOX in U_2OS/DOX,reverse MD R,and is more active than VPL and CSA.TTD may act by blocking the function of P-gp and has no effect on the expression of P-gp.