Clonorchis sinensis excretory-secretory products regulate migration and invasion in cholangiocarcinoma cells via extracellular signal-regulated kinase 1/2/nuclear factor-kappa B-dependent matrix metalloproteinase-9 expression

摘要

Matrix metalloproteinase-9 plays an important role in the invasion and metastasis of various types of cancer cells. We have previously reported that excretory-secretory products from Clonorchis sinensis increases matrix metalloproteinase-9 expression. However, the regulatory mechanisms through which matrix metalloproteinase-9 expression affects cholangiocarcinoma development remain unclear. In the current study, we examined the potential role of excretory-secretory products in regulating the migration and invasion of various cholangiocarcinoma cell lines. We demonstrated that excretory-secretory products significantly induced matrix metalloproteinase-9 expression and activity in a concentration dependent manner. Reporter gene and chromatin immunoprecipitation assays showed that excretory secretory products induced matrix metalloproteinase-9 expression by enhancing the activity of nuclear factor-kappa B. Moreover, excretory-secretory products induced the degradation and phosphorylation of I kappa B alpha and stimulated nuclear factor-kappa B p65 nuclear translocation, which was regulated by extra cellular signal-regulated kinase 1/2. Taken together, our findings indicated that the excretory-secretory product-dependent enhancement of matrix metalloproteinase-9 activity and subsequent induction of I kappa B alpha and nuclear factor-kappa B activities may contribute to the progression of cholangiocarcinoma. (C) 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.