摘要
【目的】研究苦参碱对耐药卵巢癌细胞增殖凋亡的影响并探讨其作用机制。【方法】采用MTT法检测苦参碱抑制细胞增殖的IC50;Western blotting检测细胞的Bcl-2、Bax、MDR1、MRP和LRP的蛋白表达;RT-q PCR法检测Bcl-2、Bax、MDR1、MRP和LRP的mRNA表达;流式细胞术检测细胞凋亡。【结果】苦参碱可抑制A2780/Taxol细胞增殖,且在一定浓度范围内(0.4~2 g/L)呈时间和浓度依赖性,确定最佳浓度为1/4的IC50(0.33 g/L);苦参碱可提高紫杉醇(Taxol)对A2780/Taxol细胞的抑制率,增强对紫杉醇的敏感性,逆转A2780/Taxol的耐药性;苦参碱可上调凋亡蛋白Bcl-2、Bax的mRNA和蛋白表达,下调耐药基因MDR1、MRP、LRP的mRNA和蛋白表达,抑制A2780/Taxol增殖,促进凋亡。【结论】苦参碱可逆转A2780/Taxol的耐药性,其机制可能与上调凋亡蛋白Bcl-2、Bax及下调耐药基因MDR1、MRP、LRP有关,该研究为苦参碱在耐药卵巢癌的治疗提供参考。
【Objective】To study the effect of matrine on the cell proliferation and apoptosis of drug-resistant ovarian cancer cells,and explore its mechanism.【Methods】MTT assay was used to detect the IC50 of cells by matrine.Western blotting was used to detect the protein expression of Bcl-2,Bax,MDR1,MRP and LRP.The method of RT-qPCR was used to detect the m RNA expression of Bcl-2,Bax,MDR1,MRP and LRP.Apoptosis was detected by flowcytometry.【Results】Matrine could inhibit the proliferation of A2780/Taxol cells in a time-and concentration-dependent manner(0.4-2 g/L).The optimum concentration was 1/4 IC50(0.33 g/L).Matrine significantly increased the inhibition rate of A2780/Taxol cells,and increased the sensitivity to Taxol and reversed the resistance to A2780/Taxol.Matrine could up-regulate the m RNA and protein expression of Bcl-2 and Bax,and down-regulate the m RNA and protein expression of ovarian cancer cell drug resistance genes MDR1,MRP,LRP to inhibit the A2780/Taxol proliferation and promote apoptosis.【Conclusion】Matrine can reverse the drug resistance of A2780/Taxol.The mechanism may be related to the up-regulation of apoptotic proteins Bcl-2,Bax and down-regulation of drug-resistant genes MDR1,MRP and LRP,which will provide reference for the treatment of drug-resistant ovarian cancer by matrine.
作者
胡冬梅
俞航
周浔
蔡溱
HU Dong-mei;YU Hang;ZHOU Xun;CAI Zhen(Department of Medicinal Materials Division,Changhai Hospital Affiliated to Naval Medical University,Shanghai 200433,China)
出处
《武警后勤学院学报（医学版）》
CAS
2019年第6期6-9,15,共5页
Journal of Logistics University of PAP（Medical Sciences）
作者简介
胡冬梅,大专,药师,主要从事药学方面的研究;通信作者:蔡溱,硕士,副主任药师,主要从事药学方面的研究。
