Abstract: Objective　To investigate the role of psoralen in reversing glutathione s-transferase π (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 psoralen involved in reversing GST-π mediated MDR. GST-π mediated 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.

Key words: GST-π, NF-κB, Multidrug resistance, Breast cancer, Psoralen

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。

关键词: GST-π, NF-κB, 多药耐药, 乳腺癌, 补骨脂素