The impact of transforming growth factor-β receptor Ⅱ on apoptosls and mobility in colon cancer cells with microsatellite instability
- Author:
- No author available
- Journal Title:
- Chinese Journal of Biomedical Engineering
- Issue:
- 2
- DOI:
- 10.3760/cma.j.issn.1674-1927.2012.02.005
- Key Word:
- 转化生长因子受体;结肠肿瘤;细胞迁移分析;微卫星不稳定;细胞凋亡;Transforming growth factor-β receptor;Colon neoplasms;Cell mogration assays;Microsatellite instability (MSI);Apoptosis
Abstract： Objective To investigate the impact of transforming growth factor-β receptor Ⅱ (TGFβ R Ⅱ ) expression on apoptosis and mobility of colon cancer cells with microsatellite instability (MSI).Methods Wild-type PIK3CA HCT116 cells (HCT116 wt) were selected as the colon cancer cell models with MSI.TGFβ3 R Ⅱ was then transfected into HCT116 wt cells so as to obtain HCT116 wt-R Ⅱ cells,with HCT116 wt pGenesil-NP cells as controls.Thereafter,apoptosis was induced by growth factor deprivation stress (GFDS).The expressions of phosphorylated Smad3,phosphorylated AKT,Bim2 and E-cadherin were detected by Western-blot,apoptosis of HCT116 wt-R Ⅱ cells by DNA fragmentation ELISA,and mobility of HCT116 wt-R Ⅱ cells by Transwell assay.Results TGFβ signaling pathways of HCT116 wt-R Ⅱ cells were started with TGFβ added (increased phosphorylated Smad2),which resulted in the significant restrain to GFDS- induced apoptosis and enhancement of cell mobility (both P＜0.01).PI3K inhibitor (LY294002) enabled to reverse the apoptosis-restricted and mobility-enhanced effects of TGFβ on HCT116 wt-R Ⅱ cells (P＜0.01).After the effects of TGFβ,the expressions of Bim and E-cadherin were significantly reduced (P＜0.01).Conclusion The re-expression of TGFβ R Ⅱ in colon cancer cells with MSI may increase the survival ability and mobility of colon cancer cells through PI3K/AKT pathway,which provides a molecular explanation for the favorable prognosis in patients with MSI colon cancer.
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