β1 integrin modulates tumor growth and apoptosis of human colorectal cancer

Abstract

We aimed to ascertain whether β1 integrin (ITGB1) induces apoptosis of colorectal cancer (CRC) through regulation of the mitochondrial pathway in vitro and in vivo. We generated lentiviral vectors expressing ITGB1 or ITGB1-specific RNAi and an unrelated control vector. After infection of the HT29 cells, we used western blot analysis and flow cytometric analysis to validate the patterns of ITGB1 expression. Proliferation and apoptosis were evaluated by colony formation assay, flow cytometry and western blot analysis. Upregulation of ITGB1 significantly increased the proliferation of HT29 cells; however, the levels of Bcl-2 and cyclin D1 proteins were upregulated while Bax, caspase-3, caspase-9 and p21 were downregulated in the HT29-ITGB1 cells compared to these levels in the controls. Hoechst 33258 staining and flow cytometric analysis showed that ITGB1 may play a significant role in the apoptosis of CRC cells. Moreover, ITGB1 promoted the proliferation of cells in a xenograft tumor mouse model. TUNEL staining revealed a marked increase in the percentage of positive cells in the HT29-RNAi group (84.3±4.0%), which were more significant than in the HT29- ITGB1 group (48.3±2.9%) and the other two control groups, HT29 (52.0±3.6%) and HT29-NC (49.7±4.5%). These results suggest that ITGB1 regulates the growth and apoptosis of human colorectal cancer cells.