FOXO1和Smad4对前列腺癌增殖和转移的协同抑制作用
| 作者: |
1瞿根义,
1张玉龙,
1徐勇,
1阳光,
1聂海波
1 中南大学湘雅医学院附属株洲医院泌尿外科，湖南 株洲 412007 |
| 通讯: |
徐勇
Email: tigerhnll@126.com |
| DOI: | 10.3978/j.issn.2095-6959.2020.07.001 |
| 基金: | 湖南省科技创新计划项目(2017SK51003)；株洲市科技指导性计划项目(20180004)。 |
摘要
目的：探讨FOXO1和Smad4协同抑制前列腺癌进展和转移的作用机制。方法：体外培养前列腺癌PC3细胞，采用脂质体转染方法将pEGFP-N1，pEGFP-FOXO1，pDsRed2-Smad4分别转染入PC3细胞，并依次分为pEGFP-N1组、pEGFP-FOXO1组、pDsRed2-Smad4组和pEGFP-FOXO1+pDsRed2-Smad4组4组，采用蛋白质印迹法和qPCR检测FOXO1和Smad4的蛋白和mRNA表达，CCK-8法检测细胞增殖活性，细胞划痕法检测细胞的迁移能力。结果：质粒成功转染，与pEGFP-N1组比，pEGFP-FOXO1组、pDsRed2-Smad4组和pEGFP-FOXO1+pDsRed2-Smad4组PC3细胞增殖能力、迁移能力显著降低，差异有统计学意义(P<0.05)。PC3细胞中过表达FOXO1可以上调Smad4的mRNA和蛋白表达水平，过表达Smad4可以明显增强FOXO1对PC3细胞增殖和迁移的抑制作用。结论：FOXO1与Smad4在前列腺癌中具有协同抑制前列腺癌增殖及转移的作用。
关键词：
FOXO1；Smad4；前列腺癌；协同；转移
Coordinate repression effect of FOXO1 and Smad4 on proliferation and metastasis of prostate cancer
CorrespondingAuthor: XU Yong Email: tigerhnll@126.com
DOI: 10.3978/j.issn.2095-6959.2020.07.001
Foundation: This work was supported by the Science and Technology Innovation Project of Hunan Province (2017SK51003) and Science and Technology Guiding Program of Zhuzhou City, Hunan (20180004), China.
Abstract
Objective: To investigate the mechanism of synergistic inhibition of FOXO1 and Smad4 on prostate cancer progression and metastasis. Methods: Prostate PC3 cells were cultured in vitro, and pEGFP-N1, pEGFP-FOXO1 and pDsRed2-Smad4 were transfected into PC3 cells by lipofection. They were divided into 4 groups: pEGFP-N1 group, pEGFP-FOXO1 group, pDsRed2-Smad4 group and pEGFP-FOXO1+pDsRed2-Smad4 group. The protein and mRNA expressions of FOXO1 and Smad4 were detected by Western blotting and qPCR in the group. Cell proliferation activity was detected by CCK-8 method, and cell migration ability was detected by cell scratch method. Results: The plasmid was successfully transfected. Compared with the pEGFP-N1 group, the cell proliferation and migration ability of the pEGFP-FOXO1 group, pDsRed2-Smad4 group and pEGFP-FOXO1+pDsRed2-Smad4 group were significantly decreased (P<0.05). Overexpression of FOXO1 in prostate cancer cell PC3 up-regulated the mRNA and protein expression levels of Smad4. Overexpression of Smad4 significantly enhanced the inhibitory effect of FOXO1 on proliferation and migration of PC3 cells. Conclusion: FOXO1 and Smad4 have synergistic effects in prostate cancer, synergistically inhibit prostate cancer proliferation and metastasis.
Keywords：
forkhead transcription factor O1; Smad4; prostate cancer; synergy; metastasis