实用医学杂志 ›› 2021, Vol. 37 ›› Issue (19): 2442-2446.doi: 10.3969/j.issn.1006⁃5725.2021.19.002

• 基础研究 • 上一篇    下一篇

KLF4调控TGF⁃β通路减弱EMT抑制卵巢癌细胞的增殖、侵袭及转移

王宝金1,2 徐丽达1,2 赵欣欣1,2 林少冲1,2 李霞1,2 杜俊鹏1,4 王凯2,3   

  1. 郑州大学第三附属医院1 妇科,4 小儿外科(郑州 450052);2 河南省卵巢恶性肿瘤国际联合实验室(郑州 450052);3 同济大学附属第一妇婴保健院,转化医学研究中心(上海 201204)

  • 出版日期:2021-10-10 发布日期:2021-10-10
  • 基金资助:
    河南省科技厅科技攻关重点项目(编 号 :192102310067);河南省引智项目(编号:GHB2019048)

KLF4 inhibits the proliferation,invasion and metastasis of ovarian cancer cells by regulating TGF⁃β path⁃ way to weaken EMT

WANG Baojin*,XU Lida,ZHAO Xinxin,LIN Shaochong,LI Xia,DU Junpeng,WANG Kai.   

  1. Department of Gynecology,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China *He′nan International Joint Laboratory of Ovarian Malignancies,Zhengzhou 450052,China

  • Online:2021-10-10 Published:2021-10-10

摘要:

目的 探讨 KLF4 通过调控 TGF⁃β通路减弱 EMT 对卵巢癌 SKOV3 细胞增殖、迁移及侵袭的影响。方法 构建过表达 KLF4 及空白对照组的慢病毒载体,转染卵巢癌 SKOV3 细胞,嘌呤霉素筛选后构 建空白对照组、过表达 KLF4 组卵巢癌细胞系。Western blot 法测定各组卵巢癌细胞中 TGF⁃β通路相关蛋 白及上皮⁃间质转化(EMT)相关蛋白的表达;MTT 实验检测卵巢癌细胞增殖能力的改变;Transwell 实验检 KLF4 过表达对卵巢癌细胞迁移和侵袭能力的影响;构建原位小鼠移植瘤模型,验证 KLF4 过表达对肿 瘤生长、转移的影响。结果 MTT Transwell 实验结果显示,与空白对照组相比,过表达 KLF4 组可以抑 制卵巢癌细胞的增殖、迁移和侵袭(P < 0.05);过表达 KLF4 能够明显抑制卵巢癌细胞的 EMT 过程(P < 0.05);过表达 KLF4 能通过抑制 Smad 介导的 TGF⁃β通路抑制卵巢癌细胞 EMT;KLF4 可以抑制原位小鼠卵巢癌移植瘤中原发性肿瘤生长和转移。结论 KLF4 可以通过抑制 Smad 介导的 TGF⁃β通路抑制 EMT,从而抑制卵巢癌的增殖、迁移及侵袭,KLF4/Smad/TGF⁃β/EMT 轴有望成为卵巢癌治疗的新靶点。

关键词:

卵巢癌, KLF4, Smad, TGF?β, 上皮??间质转化

Abstract:

Objective To explore the effect of KLF4 on the proliferation,migration and invasion of ovari⁃ an cancer SKOV3 cells by regulating the TGF ⁃ β pathway to attenuate EMT. Methods Lentiviral vectors of the overexpressed KLF4 and blank control groups were produced and transfected into ovarian cancer SKOV3 cells which were screened with puromycin to generate the ovarian cancer cell lines of the two groups,respectively. West⁃ ern blotting was used to determine the expression of EMT⁃related proteins in the ovarian cancer cells of each group MTT assay to detect their proliferation ability and Transwell assay to detect the effect of KLF4 overexpression on their migration and invasion ability. The orthotopic mouse xenograft model was established to verify the effect of KLF4 overexpression on the tumor growth and metastasis. Results According to MTT and Transwell,the overex⁃ pressed KLF4 in the KLF4 overexpression group significantly inhibited not only the proliferation,migration and invasion of ovarian cancer cells,but also the EMT process of ovarian cancer cells by inhibiting TGF⁃ β pathway mediated by Smad(P < 0.05),as compared with the control group. KLF4 inhibited the growth and metastasis of primary tumor in orthotopic mouse ovarian cancer xenograft. Conclusion KLF4 can inhibit EMT by inhibiting Smad mediated TGF⁃β pathway,and in this way it inhibits the proliferation of ovarian cancer,migration and inva⁃ sion. KLF4 /Smad/TGF⁃β/EMT axis is expected to be a new target for the treatment of ovarian cancer.

Key words:

ovarian cancer, KLF4, Smad, TGF?β, epithelial?mesenchymal transition