Antitumor activity of Notch‑1 inhibition in human colorectal carcinoma cells.

Abstract

This study investigated the roles of Notch-1 in colorectal carcinoma, to assess the mechanisms. The expression of Notch-1 and its ligand-Jagged1 was detected in human colorectal carcinoma, colorectal adenoma, paracancerous tissue and normal colorectal tissue by immunohistochemistry. Colorectal carcinoma cell lines were utilized to confirm the expression of Notch-1 in colorectal carcinoma cells. Lentiviral-encoding Notch-1-siRNA, as well as Notch-1 inhibitor was employed to silence Notch-1 expression and to inhibit Notch-1 activity in HT29 cells, respectively. As evidenced, Notch-1 and Jagged1 were highly expressed in colorectal carcinoma and colorectal adenoma tissues, compared with those in paracancerous tissue and normal colorectal tissue. However, the expression of Notch-1 and Jagged1 was comparable in colorectal carcinoma and colorectal adenoma tissues, and in paracancerous and normal colorectal tissues. After screening colorectal carcinoma cell lines, Notch-1 was extensively expressed in COLO 205, HT29, SW480 and SW1116 cells, but slightly expressed in LoVo cells. Subsequently, HT29 cell line was selected to investigate the roles of Notch-1 in tumor cell growth and apoptosis. Lenti-viral encoding Notch-1 siRNA significantly decreased Notch-1 expression, inhibited cell growth, arrested the cell cycle at G1 phase and promoted apoptosis. These effects were further confirmed by the Notch-1 inhibitor DAPT. Additionally, we evidenced that Notch-1 silence promoted P21 and PUMA expression in HT29 cells. Taken together, Notch-1 is an oncogene in colorectal carcinoma and the inhibition of Notch-1 could delay the cell growth and promote apoptosis in colorectal cancer.