雷公藤内酯醇—聚乙烯亚胺—环糊精复合物逆转人乳腺癌MCF-7/Taxol细胞多药耐药的作用及机制研究  

The effects and mechanisms of triptolide-polyethyleneimine-cyclodextrin complex on reversing multi-drug resistance of MCF-7/Taxol breast cancer cells

作　　者：王桂芬[1] 朱益民 李健林[1] 刘志明[1] 

机构地区：[1]广西医科大学第一附属医院胃肠腺体外科,南宁530021 [2]浙江省桐乡市第一人民医院外三科,桐乡314500

出　　处：《广西医科大学学报》2017年第5期691-694,共4页Journal of Guangxi Medical University

摘　　要：目的:观察雷公藤内酯醇—聚乙烯亚胺—环糊精复合物(TP-PEI-CyD)对人乳腺癌MCF-7/Taxol细胞多药耐药性(MDR)的作用,并探讨其可能的作用机制。方法:采用CCK-8法测定顺铂和TP-PEI-CyD对MCF-7及MCF-7/Taxol的生长抑制率,计算半数抑制浓度(IC50)、MCF-7/Taxol的耐药倍数以及TP-PEI-CyD对MCF-7/Taxol的低毒浓度。根据所得IC50,选择低毒浓度TP-PEI-CyD联合不同浓度的顺铂处理MCF-7/Taxol,测定顺铂联合TP-PEI-CyD后的IC50,并计算逆转倍数。选择低毒浓度TP-PEI-CyD联合顺铂处理MCF-7/TAXOL细胞,应用流式细胞术检测细胞凋亡情况。TP-PEI-CyD和顺铂单独或联合作用于MCF-7/Taxol后,用qPCR法检测耐药基因多药耐药相关蛋白(MRP)、肺耐药蛋白(LRP)以及谷光甘肽转移酶(GST-π)的表达水平。结果:TP-PEI-CyD对MCF-7/Taxol生长增殖有明显抑制作用,并能提高MCF-7/Taxol对顺铂的敏感性,MCF-7/Taxol耐药性得到逆转(P<0.05);顺铂联合TP-PEI-CyD作用后的细胞凋亡率明显高于顺铂组(P<0.05),同时MRP、LRP、GST-πmRNA相对表达量明显低于顺铂组和TP-PEI-CyD组(P<0.05)。结论:TP-PEI-CyD对MCF-7/Taxol有抑制增殖和诱导凋亡的作用,并能有效逆转MCF-7/Taxol细胞的肿瘤耐药性,其机制可能与下调细胞耐药基因MRP、LRP及GST-π表达水平相关。Objective： To investigate the reversal effect of triptolide-polyethyleneimine-cyclodextrin （TP-PEI-CyD） complex on multi-drug resistance in MCF-7/Taxol breast cancer ceils and its underlying mechanism. Methods： The growth inhibitory effects of cisplatin and TP-PEI-CyD on MCF-7 cells and MCF-7/Taxol cells were examined by CCK-8 assay. The IC50 values, the resistance index （RI） of cisplatin and TP-PEI-CyD on MCF-7 and MCF-7/Taxol cells, and the low-toxic concentration of TP-PEI-CyD on MCF-7/Taxol cells were calculated respectively. MCF-7/ Taxol cells were treated with low-toxic concentration of TP-PEI-CyD combined with different concentrations of cisplatin and the growth inhibitory effects were analyzed by CCK-B assay, the ICs0 value and the reversal fold were calculated accordingly. MCF-7/Taxol cells were treated with low-toxic concentration of TP-PEI-CyD combined with cisplatin, and then the apoptosis, the mRNA levels of MRP, LRP and GST-π were detected by flow cytometry and qPCR, respectively. Results： TP-PEI-CyD could significantly inhibit cell proliferation, increase the drug sensitivity to cisplatin, thus reverse the drug resistance in MCF-7/Taxol ceils （ P 〈i0.05）. The cell apoptosis rate was significant higher in cells treated with cisplatin combined with TP-PEI-CyD, while the mRNA levels of MRP, LRP and GST-π were significantly lower than those treated with TP-PEI-CyD or cisplatin alone （ P 〈0.05）. Conclusion： TP-PEI-CyD could suppress the proliferation and induce apoptosis of MCF-7/Taxol, reverse drug resistance in MCF-7/Taxol cells via down- regulating the expression of MRP, LRP and GST-π.

关 键 词：TP-PEI-CyD 顺铂 乳腺癌 耐药 逆转 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学]