薯蓣皂苷激活p38MAPK/FOXO3a信号抑制三阴性乳腺癌细胞上皮–间质转化及侵袭  

Dioscin Inhibits EMT and Invasion of Triple Negative Breast Cancer Cells via Activation of p38MAPK/FOXO3a Signaling

作　　者：方瑞[1] 赵晶晶[1] 盛飞凤[1] 肖大立[1] Fang Rui;Zhao Jingjing;Sheng Feifeng;Xiao Dali(Department of Pharmacy, Guangdong Women and Children Hospital, Guangzhou 511442, China)

机构地区：[1]广东省妇幼保健院药学部,广州511442

出　　处：《中国细胞生物学学报》2018年第5期640-647,共8页Chinese Journal of Cell Biology

基　　金：广东省自然科学基金(批准号:2016A030313785)资助的课题~~

摘　　要：该研究探讨了薯蓣皂苷(Dioscin)对三阴性乳腺癌MDA-MB-231、BT549细胞体外侵袭及上皮–间质转化(epithelial to mensenchymal transition,EMT)的影响及其作用机制。以正常人乳腺上皮MCF-10A细胞为对照,通过MTS法、克隆形成实验检测细胞增殖能力;Transwell实验检测细胞侵袭、迁移能力;Western blot法检测p38MAPK、p-p38MAPK、FOXO3a及上皮–间质转化(epithelial to mensenchymal transition,EMT)相关标志物的表达。结果显示,Dioscin能明显抑制MDA-MB-231、BT549细胞的增殖,且具有浓度依赖性,对MCF-10A细胞抑制作用较弱;Dioscin处理后肿瘤细胞的侵袭、迁移能力明显降低,Dioscin可显著下调细胞间质样标志物波形蛋白(vimentin)、N-钙黏蛋白(N-cadherin)并促进上皮样标志物E-钙黏蛋白(E-cadherin)的表达,EMT关键转录因子Snail的表达也受到抑制。进一步研究发现,Dioscin能够上调p38MAPK磷酸化水平并促进转录因子FOXO3a的表达,而干扰FOXO3a能够逆转Dioscin对细胞EMT及侵袭的抑制作用。以上研究表明,Dioscin能够抑制三阴性乳腺癌细胞EMT及体外侵袭、迁移能力,其机制可能与Dioscin调控p38MAPK/FOXO3a信号有关。The work was aimed to investigate the effect and molecular mechanism of Dioscin on invasion and epithelial to mensenchymal transition（EMT） of triple negative breast cancer cells MDA-MB-231 and BT549. Both cell lines were treated or untreated with Dioscin, normal human epithelial mammary cell line MCF-10 A was used as control. Cell proliferation was detected by MTS assay and colony formation assay. The abilities of cell invasion and migration were evaluated by Transwell assay. The expression of p38 MAPK, p-p38 MAPK, FOXO3 a, and EMT-associated biomarkers were analyzed by Western blot. The results showed that the cell proliferation was obviously reduced by Dioscin treatment in a dose dependent manner. Dioscin significantly inhibited the migration of both cells, downregulated the expression of EMT key transcription factor Snail, as well as mesenchymal makersvimentin and N-cadherin, but increased epithelial marker E-cadherin expression. Moreover, the phosphorylation level of p38 MAPK and the expression of FOXO3 a were dramatically increased upon Dioscin treatment, and knockdown of FOXO3 a reversed the inhibition effects of Dioscin on cell EMT and their invasion and migration capabilities. These above results indicated that Dioscin could inhibit proliferation and mobility of triple negative breast cancer cells in vitro, and the potential mechanism was related to activation of p38 MAPK/FOXO3 a signaling.

关 键 词：三阴性乳腺癌 薯蓣皂苷 上皮–间质转化 侵袭 P38MAPK FOXO3A 

分 类 号：R285[医药卫生—中药学]