川芎嗪逆转人乳腺癌细胞耐药株多药耐药性的实验研究

Effect of tetramethylpyrazine on reversing the multidrug resistance of human breast cancer multidrug resistant cell line induced by anticancer drugs

[目的]观察川芎嗪对抗癌剂诱导人乳腺癌细胞耐药株MCF-7/adr细胞多药耐药性的逆转作用。[方法]MTT法检测抗癌剂对乳腺癌细胞株(MCF-7)和阿霉素诱导的多药耐药细胞株(MCF-7/adr)的半数致死浓度(IC50),计算耐药指数(RI)和加川芎嗪、维拉帕米逆转剂后的逆转倍数;倒置显微镜和荧光显微镜观察川芎嗪逆转后的MCF-7/adr细胞形态;琼脂糖凝胶电泳检测川芎嗪逆转后细胞凋亡的DNA片段。[结果]对抗癌剂阿霉素、足叶乙甙、长春新碱、紫衫醇和长春花碱,MCF-7/adr细胞株的IC50均有明显增加,RI分别为145.7、41.7、72.2、488.4和286.8;加川芎嗪后IC50均有明显降低,逆转倍数分别为4.6、2.5、6.1、9.2和5.1,与逆转前相比具有统计学意义(P<0.01);荧光显微镜可观察到川芎嗪逆转后细胞凋亡的凋亡小体;琼脂糖凝胶电泳检测出川芎嗪逆转后细胞凋亡的DNA片段。[结论]川芎嗪有逆转抗癌剂诱导MCF-7/adr细胞的多药耐药性的作用。

[Objective] To explore the effect of tetramethylpyrazine on reversing the multidrug resistance of human breast cancer multidrug resistant cell line（MCF-7/adr） induced by anticancer drugs.[Methods] MTT assay was employed to test the lethal concentration 50（IC50） of MCF-7 treated by anticancer drugs and multidrug resistance subline（MCF-7/adr） induced by adriamycin（ADR） and resistance index（RI）and reverse times were calculated.The morphological changes of cultured cells were observed by inverted microscope and fluorescence microscope,and the DNA fragments of apoptosis cells treated by tetramethylpyrazine were detected with agarose gel electrophoresis assay.[Results] All of IC50 of MCF-7/adr cells treated by Adriamycin,Etoposide,Vincristine,Paclitaxel and vinblastinum were significantly increased,resistance indexes（RIs）of them were 145.7,41.7,72.2,488.4 and 286.8,respectively,then decreased after treatment of tetramethylpyrazine,reversal times were 4.6,2.5,6.1,9.2 and 5.1,respectively（P0.01）.The apoptosis body and DNA fragment caused by tetramethylpyrazine could be observed by fluorescence microscope and agarose gel electrophoresis assay.[Conclusion] Tetramethylpyrazine plays an effective role in reversal of multidrug resistance of MCF-7/adr induced by anticancer drugs.