吉祥草活性成分RCE-4抑制宫颈癌Ca Ski细胞增殖、侵袭和迁移的活性及机制研究  

Study on the activity and mechanism of RCE-4,the active ingredient of Reineckia carnea,in inhibiting the proliferation,invasion and migration of cervical cancer Ca Ski cells

作　　者：陈重旭 游方芳 金桂兰[2] 程凡 邹坤 邢翔飞[2] 奚炜[2] 陈剑锋 CHEN Chong-xu;YOU Fang-fang;JIN Gui-lan;CHENG Fan;ZOU Kun;XING Xiang-fei;XI Wei;CHEN Jian-feng(Hubei Key Laboratory of Natural Products Research and Development,College of Biological and Pharmaceutical Sciences,China Three Gorges University;The First People's Hospital of Yichang and The People's Hospital of China Three Gorges University,Yichang 443002,China)

机构地区：[1]三峡大学生物与制药学院三峡大学天然产物研究与利用湖北省重点实验室 [2]宜昌市第一人民医院,宜昌443002

出　　处：《天然产物研究与开发》2021年第9期1558-1571,共14页Natural Product Research and Development

基　　金：国家自然科学基金(81773952);湖北省卫生健康委员会中医药科研项目(ZY2019M028)。

摘　　要：本文探讨吉祥草活性单体RCE-4对宫颈癌Ca Ski细胞增殖、侵袭和迁移的影响及机制。采用MTT法和克隆形成实验检测RCE-4对Ca Ski细胞增殖的影响,划痕实验及Transwell小室实验研究RCE-4对Ca Ski细胞的迁移和侵袭的影响,间接免疫荧光实验和Western blot法检测RCE-4对β-catenin和YAP/TAZ蛋白入核转运的影响,采用Western blot法检测RCE-4对Wnt/β-catenin、Hippo/YAP信号路通及下游靶蛋白表达的影响。结果显示,RCE-4可以显著抑制Ca Ski细胞的增殖、迁移和侵袭;RCE-4处理后,β-catenin和YAP/TAZ蛋白入核减弱,GSK3β、p-β-catenin、p-YAP、p-LATS1的蛋白表达量增加,PAK4、p-GSK3β、β-catenin、MST1、LATS1、NUAK2、YAP/TAZ、YAP的蛋白表达量减少,下游靶蛋白MMPs、c-Myc、SOX2、CYR61、VCAM-1、ICAM-1的表达被抑制,提示RCE-4体外可能通过对Wnt/β-catenin和Hippo/YAP信号通路的调控发挥其抗Ca Ski细胞侵袭和迁移的作用。This article investigated the effect and mechanism of RCE-4 on proliferation,invasion and migration of cervical cancer Ca Ski cells.The effect of RCE-4 on the proliferation of Ca Ski cells was detected by MTT method and clone formation method.The scratch experiment and Transwell chamber experiment were performed to assess the effect of RCE-4 on the migration and invasion of Ca Ski cells.Indirect immunofluorescence experiment and Western blot method were used for detection.The effect of RCE-4 on the transport ofβ-catenin and YAP/TAZ proteins into the nucleus.Western blot was used to detect the effect of RCE-4 on the expression of Wnt/β-catenin,Hippo/YAP signaling pathway-related proteins and downstream target proteins.The results showed that RCE-4 can significantly inhibit the proliferation,migration and invasion of Ca Ski cells;after RCE-4 treatment,β-catenin and YAP/TAZ proteins enter the nucleus attenuated,and the protein expression of GSK3β,p-β-catenin,p-YAP,p-LATS1 increased,and the protein expression of PAK4,β-catenin,MST1,LATS1,NUAK2,YAP/TAZ,and YAP were decreased,and the expression of the downstream target proteins MMPs,c-Myc,SOX2,CYR61,VCAM-1,ICAM-1 were inhibited,suggesting that RCE-4 may exert its anti-Ca Ski cell invasion and migration effects through regulation of Wnt/β-catenin and Hippo/YAP signaling pathways in vitro.

关 键 词：RCE-4 侵袭 迁移 WNT/Β-CATENIN Hippo/YAP 

分 类 号：R966[医药卫生—药理学]