雷公藤内酯醇-聚乙烯亚胺-环糊精对乳腺癌多药耐药细胞MCF-7/Taxol逆转作用的研究  

Effects and mechanisms of triptolide-polyethylenimine-cyclodextrin reversing the multidrug resistance of MCF-7/Taxol in breast cancer

作　　者：王桂芬[1] 李健林[1] 王慧慧[1] 朱益民 

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530000 [2]浙江省桐乡市第一人民医院外三科,314500

出　　处：《中华普通外科学文献（电子版）》2017年第3期159-163,共5页Chinese Archives of General Surgery(Electronic Edition)

基　　金：浙江省级公益性技术应用研究计划项目(2014C33259);自噬影响三阴性乳腺癌对多西他赛敏感性的研究项目(2015GXNSFAA39225)

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-Cy D)对乳腺癌细胞MCF-7/Taxol耐药性的逆转作用并探讨其可能的作用机制。方法 CCK-8法测紫杉醇和TPPEI-Cy D对MCF-7及MCF-7/Taxol的生长抑制率,计算出各自的IC50值、MCF-7/Taxol的耐药倍数以及TP-PEI-Cy D对MCF-7/Taxol的低毒浓度;根据所得IC50值选择低毒浓度TP-PEI-Cy D联合不同浓度的紫杉醇处理MCF-7/Taxol后,测得紫杉醇联合TP-PEI-Cy D后的IC50,并计算逆转倍数;选择低毒浓度TP-PEI-Cy D联合紫杉醇处理MCF-7/Taxol细胞后,应用流式细胞术测细胞凋亡情况;TP-PEI-Cy D和紫杉醇单独或联合分别作用于MCF-7/Taxol,用RT-PCR检测耐药基因多药耐药相关蛋白(MRP)、肺耐药蛋白(LRP)以及谷胱甘肽转移酶(GST-π)的表达水平。结果 TP-PEICy D对MCF-7/Taxol生长增殖有明显抑制作用,并提高MCF-7/Taxol对紫杉醇的敏感度,MCF-7/Taxol耐药性得到逆转(F=439.36,P<0.01);紫杉醇联合TP-PEI-Cy D的细胞凋亡率明显高于紫杉醇单独用药(F=17.91,P<0.05)。联合使用后MRP、LRP、GST-πmRNA表达水平降低(F=27.41、33.99、20.77,均P<0.01)。结论 TP-PEI-Cy D对MCF-7/Taxol有增殖抑制和诱导凋亡作用,能有效逆转MCF-7/Taxo细胞的肿瘤耐药性,其机制可能与降低细胞耐药基因LRP、MRP以及GST-πmRNA表达水平相关。Objective To investigate the reversal effect of triptolide-polyethylenimine-cyclodetrin （TP-PEI-CyD） on multidrug resistance in human breast cancer cells （MCF-7/Taxol） and its underlying mechanism.Methods The inhibitory effects of Taxol and TP-PEI-CyD on growth of MCF-7 cells and MCF-7/Taxol cells were examined by CCK-8 assay and their IC50 values and the resistance index （RI） of MCF-7/Taxol cells and the low-toxic concentration of TP-PEI-CyD inhibiting the growth of MCF-7/Taxol cells were calculated. Based on the IC50 results, MCF-7/Taxol cells were treated with a selected low-toxic concentration of TP-PEI-CyD combined with different concentrations of Taxol and detected by CCK-8 assay, and then the IC50 and reverse times were calculated. MCF-7/Taxol cells were treated with a selected low-toxic concentration of TP-PEI-CyD and Taxol combined, and then the influence on doxorubicin-induced apoptosis, and the expressions of the mRNA of multidrug resistance protein （MRP）,lung resistance protein （LRP） and glutathione S-transferase-π （GST-π） were detected by flow cytometry and RT-PCR, respectively.Results TP-PEI-CyD in combination with Taxol significantly inhibited cell proliferation （F=439.36,P〈0.01） and induced apoptosis with an increase in MCF-7/Taxol cells when compared to TP-PEI-CyD or Taxol used alone （F=17.91,P〈0.05）.MCF-7/Taxol cells received TP-PEI-CyD in combination with Taxol treatmental also had a lower expression level of MRP、LRP and GST-πmRNA （F=27.41, 33.99, 20.77, allP〈0.01）.Conclusion TP-PEI-CyD can suppress the proliferation, induce apoptosis of MCF-7/Taxol, and reverse MDR in MCF-7/Taxol cells, its mechanism might be related to reduce the mRNA expression of MRP, LRP and GST-π.

关 键 词：雷公藤属 乳腺肿瘤 多药耐药相关蛋白质类 逆转 紫杉醇 

分 类 号：R737.9[医药卫生—肿瘤]