Notch1 silencing inhibits proliferation and invasion in SGC­7901 gastric cancer cells.

ABSTRACT

Downregulation of Notch1 has been shown to exert antineoplastic effects in vivo and in vitro. However, the role of the Notch1 gene in the proliferative and invasive ability of gastric cancer cells is not clear. In this study, we investigated the effect of Notch1 gene silencing on the proliferation and invasion of gastric cancer SGC­7901 cells. Small interfering RNA (siRNA) targeting Notch1 was transfected into SGC­7901 cells using Lipofectamine 2000. Proliferation of SGC­7901 cells was then determined by the MTT assay. Notch1 mRNA expression was determined by reverse transcription­polymerase chain reaction (RT­PCR). Invasion of the SGC­7901 cells was detected by the Transwell assay. The protein levels of cyclin D1, cyclin A1 and cyclin-dependent kinase 2 (CDK2) were determined by western blotting. The mRNA levels of matrix metalloproteinase­2 (MMP­2) and cyclooxygenase­2 (COX­2) were determined by RT­PCR. Compared to the control group, the Notch1 mRNA level was significantly decreased following transfection. The growth and invasion rates of SGC­7901 cells were significantly reduced after Notch1 silencing. Additionally, the expression of cyclin D1 and cyclin A1 proteins and of the MMP­2 and COX­2 mRNAs was markedly attenuated. From these results, it was concluded that Notch1 gene silencing inhibits the proliferation of gastric SGC­7901 cells by decreasing the expression of cyclins D1 and A1, and reduces the invasive ability of SGC­7901 cells through the downregulation of MMP­2 and COX­2 genes. Thus, silencing of the Notch1 pathway may be a novel approach in the treatment of gastrointestinal cancer.