淫羊藿素通过Hedgehog信号通路抑制基底细胞癌细胞生存和迁移  

Icaritin inhibits survival and migration of basal cell carcinoma cells through Hedgehog signaling pathway

作　　者：胡文龙 吴平平 刘灵花 刘友饶 HU Wen-long;WU Ping-ping;LIU Ling-hua;LIU You-rao(Jiujiang University Affiliated Hospital,Jiujiang 332000,China)

机构地区：[1]九江学院附属医院,九江332000

出　　处：《天然产物研究与开发》2022年第7期1091-1097,1155,共8页Natural Product Research and Development

基　　金：国家自然科学基金(81760166);江西省教育厅科学技术研究项目(GJJ190926);江西省中医药管理局科技计划(2020A0344)。

摘　　要：本文旨在探讨淫羊藿素对基底细胞癌A431细胞的抑制作用及可能的机制。将不同浓度淫羊藿素和/或GANT 61作用于A431细胞,采用CCK-8法检测细胞活性,Transwell实验检测细胞迁移能力,qPCR及Western blot检测Hedgehog、Smo、Gli1、Bcl-2、Bax和MMP-9的表达情况,Caspase-3活性检测和流式细胞术检测淫羊藿素和/或GANT 61对细胞凋亡的影响。结果显示,淫羊藿素和GANT 61均能明显抑制A431细胞的活性,下调Hedgehog、Smo、Gli1、Bcl-2和MMP-9的表达,上调Bax的表达,增强Caspase-3活性,介导凋亡,抑制细胞迁移能力,而淫羊藿素并不能在GANT 61的基础上进一步增强上述作用。上述结果提示,淫羊藿素可能主要通过抑制刺猬(Hedgehog,Hh)信号通路,促进凋亡相关因子的表达,介导基底细胞癌细胞凋亡,下调MMP-9的表达,抑制基底细胞癌细胞的迁移。The purpose of the present study was to investigate the effect and its mechanism of icaritin on basal cell carcinoma cell line A431.A431 cells were treated with icaritin at different concentrations and/or GANT 61.The viability and migration of A431 cells were assayed by CCK-8 method and Transwell assay.The expression of Hedgehog,Smo,Gli1,Bcl-2,Bax and MMP-9 was detected by qPCR and Western blot.Flow cytometry and Caspase-3 activity assay were used to investigate the effects of icaritin and/or GANT 61 on apoptosis of cells.The results showed that,both icaritin and GANT 61 could significantly inhibit the viability of A431 cells,down-regulate the expression of Hedgehog,Smo,Gli1,Bcl-2,MMP-9 and up-regulate the expression of Bax,enhance the activity of Caspase-3 and mediated the apoptosis,inhibited the migration of A431 cells.However,icaritin could not enhance these effects on the basis of Gant 61.Icaritin could promote apoptosis and inhibit migration by Hedgehog signaling pathway in basal cell carcinoma cells.These results suggest that icaritin may promote the expression of apoptotic-related factors,and mediate the apoptosis,down-regulate the expression of MMP-9,and inhibit the migration of basal cell carcinoma cells mainly by inhibiting Hedgehog signaling pathway.

关 键 词：淫羊藿素 基底细胞癌 HEDGEHOG信号通路 凋亡 迁移 

分 类 号：R285.5[医药卫生—中药学]