Antitumor activity of Notch-1 inhibition in human colorectal carcinoma cells
نویسندگان
چکیده
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.
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