摘要
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Rh123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。
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 enhance doxorubicin cytotoxicity was tested using MTT F3-（4, 5 dimethylthiazol） 2,5-diphenyhetrazolium bromide] assay and evaluated by the reversal fold （RF） values. The level of P-glycoprotein （P-gp） expression 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 concentration of 10μg/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 isotetrandrine, which indicated that the function of P-gp was effectively inhibited. Conclusion Isotetrandrine exhibited 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.
出处
《肿瘤防治研究》
CAS
CSCD
北大核心
2009年第1期1-4,共4页
Cancer Research on Prevention and Treatment
基金
河南大学自然科学基金(06YBZR077)
关键词
异汉防己碱
阿霉素
肿瘤细胞
多药耐药性
Isotetrandrine
Doxorubicin
Tumor cells
Multidrug resistance introduction
