补骨脂素逆转GST-π介导的多药耐药的 研究  

Effect of psoralen in reversing GST-π mediated multidrug resistance

作　　者：花义同 侯长冉 张浩杰 杲霄源 Hua Yitong;Hou Changran;Zhang Haojie;Gao Xiaoyuan(Department of Breast Surgery,Binzhou Medical University Hospital,Binzhou 256600,China)

机构地区：[1]滨州医学院附属医院乳腺外科,滨州256600

出　　处：《国际医药卫生导报》2022年第15期2084-2088,共5页International Medicine and Health Guidance News

基　　金：国家自然科学基金项目(81173601,30972932);山东省高等学校科技计划项目(J15LL51);山东省自然科学基金项目(ZR2014HQ020);滨州医学院科技计划项目(BY2017KJ01);滨州医学院科研计划与科研启动基金(BY2014KYQD36)。

摘　　要：目的探讨补骨脂素在逆转谷胱甘肽s-转移酶π(GST-π)介导的多药耐药中的作用,以及在MCF-7/ADR细胞中的可能机制。方法研究时间:2015年至2020年。采用CCK-8法检测细胞活力,评价补骨脂素的细胞毒性和多药耐药逆转活性。采用实时聚合酶链反应(RT-PCR)检测GST-π的表达,检测靶基因的变化。采用免疫印迹法检测GST-π蛋白水平。采用免疫荧光法观察核因子κB(NF-κB)的活化情况。组间比较采用独立样本t检验,P<0.05为差异有统计学意义。结果应用补骨脂素处理后,细胞内阿霉素药物浓度明显升高。与对照组相比,补骨脂素降低了治疗组GST-π在基因和蛋白水平上的表达。NF-κB抑制剂(SN50)可显著抑制乳腺癌MCF-7/ADR细胞中GST-π的表达。结论NF-κB信号通路可能是GST-π介导的多药耐药发病机制之一。补骨脂素参与了逆转GST-π介导的多药耐药。GST-π介导的耐药机制可能与NF-κB信号通路有关,是NF-κB信号通路下游的关键因子。Objective To investigate the role of psoralen in reversing glutathione s-transferaseπ(GST-π)mediated multidrug resistance(MDR)and the possible mechanism in MCF-7/ADR cells.Methods The research time was from 2015 to 2020.We measured the cell viability by CCK-8 assay to evaluate the cytotoxicity and MDR reversal activity of psoralen.The alteration in targeted genes was examined.The real-time polymerase chain reaction(RT-PCR)was used to detect the expression of GST-π.Western blot was used to analyze the level of GST-π protein.The immunofluorescence method was applied to observe the activation of NF-κB.The measurement data were compared by the independent-sample t test.If P<0.05.there is a statistical difference.Results The intracellular adriamycin drug concentration increased significantly after psoralen treatment.Compared with those of the control group,psoralen reduced the expression of GST-π on the mRNA and protein levels in the treatment group.The NF-κB inhibitor(SN50)could significantly inhibit the expression of GST-π in breast cancer MCF-7/ADR cells.Conclusions NF-κB signaling pathway may be one of the mechanisms of GST-π mediated MDR.Our results showed that psoraleninvolved in reversing GST-π mediated MDR.GST-πmediated drug resistance mechanism may be related to the NF-κB signaling pathways,and it may be the key factor of downstream in the NF-κB signaling pathways.

关 键 词：GST-Π NF-ΚB 多药耐药 乳腺癌 补骨脂素 

分 类 号：R965[医药卫生—药理学]