VERU-111通过TGF-β通路调控EMT抑制卵巢癌细胞的增殖及转移  

VERU-111 regulates EMT through the TGF-βpathway and inhibits the proliferation and metastasis of ovarian cancer cells

作　　者：王宝金[1] 刘子平 赵欣欣 张志广 张瑞涛[2] 王蕾[3] 吴鑫鑫 WANG Baojin;LIU Ziping;ZHAO Xinxin;ZHANG Zhiguang;ZHANG Ruitao;WANG Lei;WU Xinxin(Department of Gynecology and Obstetrics,Third Affiliated Hospital,Zhengzhou University,Zhengzhou 450052,China;Department of Gynecology and Obstetrics,First Affiliated Hospital,Zhengzhou University,Zhengzhou 450000,China;School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]郑州大学第三附属医院妇科,郑州450052 [2]郑州大学第一附属医院妇产科,郑州450000 [3]郑州大学药学院,郑州450001

出　　处：《药学前沿》2025年第3期374-380,共7页China Pharmacist

基　　金：河南省高等学校重点科研项目(25A320013);河南省科技攻关项目(242102520028)。

摘　　要：目的探讨微管抑制剂VERU-111通过调控转化生长因子β(TGF-β)通路抑制上皮-间质转化(EMT),从而降低卵巢癌细胞的增殖及转移能力的作用机制。方法以卵巢癌细胞系OVCAR3和SKOV3为研究对象,将细胞分为对照组、VERU-111低剂量组、VERU-111高剂量组及TGF-β激活剂组。通过MTT法测定细胞增殖能力、克隆形成实验评估细胞克隆能力及迁移实验分析细胞迁移特性。Western blotting实验检测TGF-β信号通路相关蛋白及EMT标志蛋白的表达水平。结果与对照组相比,VERU-111处理组的OVCAR3和SKOV3卵巢癌细胞的增殖、克隆形成及迁移能力显著下降(P<0.05)。此外,VERU-111显著抑制了TGF-β及其下游通路中关键蛋白(如Smad2/3)的磷酸化水平,同时减少了EMT间质标志蛋白(如N-钙黏蛋白和波形蛋白)的表达,并增加了上皮标志蛋白E-钙黏蛋白的表达(P<0.05)。结论微管抑制剂VERU-111通过调控TGF-β通路抑制EMT过程,显著减弱卵巢癌细胞OVCAR3和SKOV3的增殖及迁移能力,具有潜在的治疗应用价值。Objective To investigate the mechanism by which the microtubule inhibitor VERU-111 inhibits epithelial-mesenchymal transition(EMT)through regulation of the transforming growth factor-β(TGF-β)pathway,thereby reducing the proliferation and metastasis of ovarian cancer cells.Methods Ovarian cancer cell lines OVCAR3 and SKOV3 were used as research subjects.The cells were divided into four groups:the control group,the low-dose VERU-111 group,the high-dose VERU-111 group,and TGF-β activator group.Cell proliferation was assessed using the MTT assay,colony formation assay was used to evaluate clonogenic ability,and migration assay was used to analyze cell migratory characteristics.Western blotting was used to detect proteins related to the TGF-β signaling pathway and EMT markers.Results Compared with the control group,VERU-111 treatment significantly reduced the proliferation,colony formation,and migration abilities of OVCAR3 and SKOV3 ovarian cancer cells(P<0.05).Additionally,VERU-111 markedly inhibited the phosphorylation levels of key proteins in the TGF-β and its downstream signaling pathways,such as Smad2/3,and decreased the expression of mesenchymal markers,such as N-cadherin and vimentin.It also increased the expression of the epithelial marker E-cadherin(P<0.05).Conclusion The microtubule inhibitor VERU-111 significantly suppresses the proliferation and migration of ovarian cancer cells OVCAR3 and SKOV3 by regulating the TGF-β pathway to inhibit the EMT process,suggesting its potential therapeutic application value.

关 键 词：微管抑制剂 VERU-111 转化生长因子Β 上皮-间质转化 卵巢癌 

分 类 号：R966[医药卫生—药理学]