Abstract:

Background and purpose: Esophageal carcinoma is one of main malignancies with rapid course and a poor prognosis in China. The reasons of poor overall survival are the invasion and metastasis of the tumor. Matrix metalloproteinase (MMPs) play essential roles in promoting tumor invasion and metastasis. In this study, we aimed to investigate the expression and functional significance of matrix metalloproteinase 16(MMP-16) in esophageal squamous cell carcinoma (ESCC). We expect to find a lead molecule for the benefit of early detecting tumor and the development of novel treatment of ESCC. Methods: The expression levels of MMP-16 protein and mRNA in human ESCC and the matched normal tissues were determined by immunohistochemistry, Western blot and Real-Time PCR (RT-PCR). The stable Ec109 cell line with MMP-16 knockdown and negative controls were established by RNA interference technology. The cell migration, invasion, proliferation and cell apoptosis of MMP-16 in stable interfered Ec109 cell line was examined by cell counting, scratch test, Transwell test and flow cytometry assays. The data were analyzed by t test. Results: MMP-16 protein was downregulated in cancerous group compared with the matched normal tissue and correlated with the clinical features of histological differentiation (P<0.05) and tumor stage (P<0.05). The levels of MMP-16 mRNA and protein in Ec109 were significantly decreased by RNA intetrence (P<0.05). We demonstrated that MMP-16 silencing significantly promoted cell invasion and migration (P<0.05), and inhibited cell apoptosis (P<0.05), while no significant effect was observed on cell proliferation (P>0.05). Conclusion: MMP-16 is downregulated in human ESCC tissues. The cell migration and invasion is promoted by interference of MMP-16 in Ec109, while the cell apoptosis is inhibited. MMP-16 may be considered as a target gene for therapy of ESCC.

Key words: Esophageal squamous cell carcinoma, Matrix metalloproteinase-16, RNA interference, Invasion, Migration