汉黄芩素通过Hippo-YAP1信号通路调控胆囊癌细胞增殖和凋亡的机制  

Mechanism of wogonin regulating the proliferation and apoptosis of gallbladder cancer cells through Hippo-YAP1 signal pathway

作　　者：陶英奇 李少一 廖勇 TAO Ying-qi;LI Shao-yi;LIAO Yong(Department of Hepatobiliary Surgery,Xingtai People's Hospital Affiliated to Hebei Medical University,Xingtai 054000,China)

机构地区：[1]河北医科大学附属邢台市人民医院肝胆外科,河北邢台054000

出　　处：《中国现代普通外科进展》2023年第11期847-851,856,共6页Chinese Journal of Current Advances in General Surgery

基　　金：2020年邢台市市级科技计划自筹经费项目(2020ZC273)。

摘　　要：目的:探讨汉黄芩素(WOG)调节Hippo-YAP1信号通路对胆囊癌细胞恶性生物学行为的作用机制。方法:将GBC-SD细胞分为正常组(Control组)、汉黄芩素低、中、高剂量组(WOG-L、M、H组,汉黄芩素20、50、100μmol/L)、吉西他滨组(吉西他滨4 mg/L)。CCK-8法检测细胞增殖活性;划痕实验和Transwell实验检测细胞侵袭能力;小管形成实验检测细胞血管形成能力;流式细胞仪检测细胞凋亡;Western blot法检测蛋白表达。结果:与Control组比较,WOG各剂量组和吉西他滨组细胞增殖活性及增殖蛋白CyclinD1表达,迁移和侵袭能力及蛋白MMP12、MMP9、MMP14表达,细胞血管形成能力,抗凋亡蛋白Bcl-2,Hippo-YAP1通路蛋白p-MST1、YAP1表达显著下降(P<0.05);细胞凋亡率,促凋亡蛋白Bax、Cleaved-caspase3表达,Hippo-YAP1通路蛋白MST1、p-YAP1蛋白表达显著上升(P<0.05);吉西他滨组与WOG-H组细胞上述指标差异无统计学意义(P>0.05)。结论:WOG可以调节Hippo-YAP1通路中MST1表达量,抑制YAP1磷酸化表达,从而抑制胆囊癌GBC-SD细胞增殖、迁移侵袭和血管形成,促进GBC-SD细胞凋亡。Objective:To investigate the mechanism of wogonin(WOG)on the malignant biological behavior of gallbladder cancer cells by regulating Hippo YAP1 signal pathway.Methods:GBC-SD cells were divided into normal group(Control group),low,medium and high dose wogonin groups(WOG-L,M,H groups,wogonin 20,50,100μmol/L),and gemcitabine group(gemcitabine 4 mg/L).Cell proliferation activity was detected by CCK8 method;scratch test and Transwell test were used to detect the migration and invasion abilities of cells;the ability of cell angiogenesis was detected by tubule formation test;apoptosis was detected by flow cytometry;the protein expression was detected by Western blot.Results:Compared with the Control group,the cell proliferation activity,the expression of cyclin D1,the migration and invasion abilities,the expression of MMP12,MMP9,MMP14,the ability of cell angiogenesis,the expression of anti apoptotic protein Bcl-2,Hippo YAP1 pathway proteins p-MST1,and YAP1 were obviously decreased in the WOG dose groups and gemcitabine groups,the rate of cell apoptosis,the expression of pro apoptotic proteins Bax,Cleaved-caspase 3,the Hippo YAP1 pathway protein MST1 P-YAP1 protein were obviously increased(P<0.05);there was no obvious difference in the above indicators between gemcitabine group and WOG-H group(P>0.05).Conclusion:WOG can regulate the expression of MST1 in Hippo YAP1 signal pathway,inhibit the expression of YAP1 phosphorylation,t hus inhibit the proliferation,migration,invasion and angiogenesis of GBC-SD cells,and promote the apoptosis of GBC-SD cells.

关 键 词：胆囊肿瘤 汉黄芩素 细胞增殖 细胞凋亡 Hippo-YAP1信号通路 

分 类 号：R285[医药卫生—中药学] R735.8[医药卫生—中医学]