Knockdown of MMP-7 inhibits cell proliferation and enhances sensitivity to 5-fluorouracil and X-ray irradiation in colon cancer cells.

The role of matrix metalloproteinase-7 (MMP-7) in the pathogenesis of colon cancer is not understood thoroughly. Previous studies from our group have shown that the expression levels of MMP-7 were highly elevated in colorectal cancer patient specimens and were correlated with Dukes Staging, histological differentiation grade and CEA level. The goal of this study was to investigate the cellular impact of MMP-7 in colon cancer. In this study, we used the SW480 colon cancer cell lines of MMP-7 knockdown by lentivirus-mediated RNA interference as a model system to investigate the impact of MMP-7 on cell proliferation and sensitivity to 5-Fluorouracil (5-FU) and X-ray irradiation (IR). Cell proliferation and sensitivity to 5-FU and IR were measured by MTT assay and colony formation assay. Cell cycle was evaluated by flow cytometry. We showed that the down regulation of MMP-7 inhibits colon cancer cell proliferation and sensitizes tumour cells to 5-FU and IR ( P < 0.05). Decreased MMP-7 expression in SW480 cells by RNA interference triggered cell cycle arrest at G1 phase ( P < 0.05). Down regulation of MMP-7 may inhibit the cell proliferation of colon cancer cells and increase tumour cells sensitivity to radiotherapy and chemotherapy. RNAi-mediated silencing of MMP-7 may represent a powerful therapeutic approach for controlling human colorectal cancer growth. [ABSTRACT FROM AUTHOR]