基于Hedgehog通路探究防己诺林碱对三阴性乳腺癌抗肿瘤机制的实验研究

Anti-tumor Mechanism of Fangchinoline in Triple Negative Breast Cancer Based on Hedgehog Signaling Pathway

[目的]探究防己诺林碱对三阴性乳腺癌抗肿瘤机制。[方法]MTT法检测防己诺林碱对三阴性乳腺癌细胞的抑制率,计算IC50;细胞流式实验观察防己诺林碱对三阴性乳腺癌细胞的凋亡影响;Western blot法探究防己诺林碱对Smo及Gli1蛋白表达的影响。[结果]防己诺林碱对三阴性乳腺癌细胞BT549的活力有影响,IC50值为8.99μmol/L。随着防己诺林碱浓度升高细胞凋亡率增加,三阴性乳腺癌细胞BT549通路Hedgehog中的Smo、Gli1蛋白表达水平明显降低(P<0.05)。FAN可以抑制肿瘤的生长。[结论]防己诺林碱可通过下调细胞凋亡相关信号通路Hedgehog来影响三阴性乳腺癌细胞凋亡,同时影响三阴性乳腺癌肿瘤的生长。

[Objective] To explore the anti-tumor mechanism of Fangchinoline in triple negative breast cancer based on hedgehog signaling pathway.[Methods] Three negative breast cancer（TNBC） BT549 cells were treated with fangchinoline.The inhibition rate of BT549 cells was detected by MTT and IC50 was calculated;the cell apoptosis was detected by flow cytometry.The expression of Smo and Gli1 protein was detected by Western blot.[Results] Fangchinoline inhibited the proliferation of BT549 cells with a IC50 of 8.99μmol/L.Flow cytometry showed that Fangchinoline induced the apoptosis of BT549 cells in a dose-dependent manner.The expression of Smo and Gli1 in the BT549 cells was declined with the increasing Fangchinoline concentration.Fangchinoline also inhabited the growth of BT549 breast cancer grafts in tumor-bearing nude mice.[Conclusion] Fangchinoline inhibits cell growth and enhances cell apoptosis of TNBC cells in vitro and in vivo,which may be associated with the regulation by hedgehog signaling pathway.