异汉防己碱增强多药耐药肿瘤细胞对阿霉素的敏感性及其机制

目的:以K562/DOX和MCF-7/DOX细胞为对象，探讨异汉防己碱对化疗药物阿霉素（DOX）的增敏作用及其作用机制。方法:采用MTT法检测异汉防己碱的内在细胞毒性及其对阿霉素的增敏作用，并以RF值评价其增敏效果。应用流式细胞术（FCM）检测细胞膜上P-gp的表达以及细胞内DOX和罗丹明123（Rh123）的蓄积量。结果:异汉防己碱在10μg/ml的无毒剂量可明显增强DOX的细胞毒性。K562/DOX和MCF-7/DOX细胞膜上P-gp均呈强阳性表达，但异汉防己碱对该P-gp表达水平无明显影响。异汉防己碱可使K562/DOX和MCF-7/DOX细胞内DOX和123的荧光密度（FI）均明显增加，由此证明异汉防己碱可有效抑制P-gp的功能。结论:异汉防己碱可通过抑制P-gp的功能而增强阿霉素的敏感性，从而有效逆转肿瘤细胞的多药耐药性（MDR），它可能成为有效多药耐药逆转剂的候选药物。

Effect and Mechanism of Isotetrandrine to Enhance Doxorubicin Sensitivity in Multidrug Resistance Tumor Cells

Objective To explore the effect and mechanism of Isotetrandrine to enhance doxorubicin (DOX) sensitivity of K562/DOX and MCF-7/DOX cells. Methods The activity of Isotetrandrine to en-hance doxorubicin cytotoxicity was tested using MTT -3-(4, 5-dimethylthiazol)-2,5-diphenyltetrazolium bromide] assay and evaluated by the reversal fold (RF) values. The level of P-glycoprotein (P-gp) ex-pression and intracellular accumulation of doxorubicin and rhodamine123 (Rh123) were assessed by flow cytometry (FCM). Results The doxorubicin-induced cytotoxicity was significantly potentiated by isotet-randrine with the eoneentration of 10 μg/ml. P-gp was expressed in both K562/DOX cells and MCF-7/DOX cells, but the level of P-gp expression was not distinct difference at the absence or presence of iso-tetrandrine. The intracellular accumulation of DOX and Rh123 was increased in the presence of isotetran-drine, which indicated that the function of P-gp was effectively inhibited. Conclusion Isotetrandrine ex-hibited potent effect in the reversal of tumor multidrug resistance (MDR) by inhibiting the function of P-gp in vitro, suggesting that it may become a candidate of effective MDR reversing agents in cancer chem-otherapy.