中国组织化学与细胞化学杂志2024,Vol.33Issue(3) :217-224.DOI:10.16705/j.cnki.1004-1850.2024.03.002

TIPE1抑制结直肠癌细胞增殖、迁移、侵袭、上皮间质转化和TGF-β/Smad信号

TIPE1 inhibits proliferation,migration,invasion,epithelial-mesenchymal transformation and TGF-β/Smad signaling of colorectal cancer cells

袁博 马磊 陈小兵 常占国
中国组织化学与细胞化学杂志2024,Vol.33Issue(3) :217-224.DOI:10.16705/j.cnki.1004-1850.2024.03.002

TIPE1抑制结直肠癌细胞增殖、迁移、侵袭、上皮间质转化和TGF-β/Smad信号

TIPE1 inhibits proliferation,migration,invasion,epithelial-mesenchymal transformation and TGF-β/Smad signaling of colorectal cancer cells

袁博 1马磊 2陈小兵 3常占国1
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作者信息

  • 1. 南阳第一人民医院肿瘤血液科,南阳 473000
  • 2. 南阳市第一人民医院肿瘤科,南阳 473000
  • 3. 河南省肿瘤医院消化肿瘤内科,南阳 450000
  • 折叠

摘要

目的 探索肿瘤坏死因子α诱导蛋白8样分子1(tumor necrosis factorα-induced protein 8-like 1,TIPE1)对结直肠癌细胞增殖、迁移、侵袭和上皮-间质转化(EMT)的影响,并分析其可能的生物学机制.方法 RT-qPCR检测结直肠癌组织和细胞株中TIPE1 mRNA水平.用慢病毒稳定转染法过表达TIPE1后,用CCK-8法检测结直肠癌细胞的细胞活力,划痕愈合实验和Transwell实验检测细胞的迁移和侵袭,Western blot实验检测细胞中TGF-β/Smad/EMT信号相关蛋白的表达.在裸鼠皮下种植过表达TIPE1的SW480细胞,种植21 d后处死动物,测量肿瘤的体积,并用免疫组织化学染色检测TGF-β/Smad/EMT信号相关蛋白的表达.结果 结直肠癌组织和细胞中TIPE1 mRNA表达下调.对结直肠癌细胞过表达TIPE1后,细胞的活力、迁移和侵袭的能力下降.Western blot实验结果显示,过表达TIPE1后,结直肠癌细胞中E-cadherin的水平增加,vimentin的水平下降,TGF-β1和p-Smad2的水平降低.裸鼠实验显示,TIPE1过表达组瘤体生长缓慢且体积变小;免疫组织化学染色显示,TIPE1过表达组的瘤体中E-cadherin表达上调,vimentin、TGF-β1和p-Smad2表达下调.结论 过表达TIPE1可抑制结直肠癌细胞增殖、迁移、侵袭与EMT,这其中可能至少涉及到抑制TGF-β/Smad信号活性.

Abstract

Objective To investigate the effects of tumor necrosis factor α-induced protein 8-like 1 (TIPE1) on the proliferation,migration,invasion,and epithelial-mesenchymal transition (EMT) of colorectal cancer (CRC) cells and to analyze its potential biolog-ical mechanisms.Methods RT-qPCR was used to measure TIPE1 mRNA levels in CRC tissues and cell lines.After over-expressing TIPE1 using lentiviral transduction,cell viability was assessed using the CCK-8 assay,while wound healing and Transwell assays were performed to evaluate cell migration and invasion.Western blotting was employed to detect the expression of proteins related to TGF-β/Smad/EMT signaling in the cells.Subcutaneous xenografts were established by injecting SW480 cells over-expressing TIPE1 into nude mice.Animals were sacrificed after 21 days,and tumor volumes were measured.Immunohistochemical staining was used to analyze the expression of TGF-β/Smad/EMT signaling-related proteins in tumor tissues.Results TIPE1 mRNA expression was down-regulated in CRC tissues and cells.Over-expression of TIPE1 in CRC cells reduced cell viability,migration,and invasion.Western blot results showed that over-expression of TIPE1 increased E-cadherin levels while decreasing vimentin,TGF-β1,and p-Smad2 levels in CRC cells.In the nude mouse model,the TIPE1 overexpression group exhibited slower tumor growth and smaller tumor volumes.Immunohistochemical staining showed upregulated E-cadherin and downregulated vimentin,TGF-β1,and p-Smad2 in tumors from the TIPE1 over-expression group.Conclusion Over-expression of TIPE1 inhibits CRC cell proliferation,migration,invasion,and EMT,potentially through suppression of TGF-β/Smad signaling activity.

关键词

结直肠癌/肿瘤坏死因子α诱导蛋白8样分子1/上皮-间质转化/迁移/侵袭/TGF-β/Smad信号

Key words

Colorectal cancer/tumor necrosis factor α-induced protein 8-like 1/epithelial-mesenchymal transition/migration/invasion/TGF-β/Smad signaling

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出版年

2024
中国组织化学与细胞化学杂志
中国解剖学会,华中科技大学同济医学院

中国组织化学与细胞化学杂志

CSTPCD
影响因子:0.476
ISSN:1004-1850
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