Clonorchis sinensis (C. sinensis) infection is known to cause cholangiocarcinomas in humans, but the mechanism is not clearly understood. In order to verify the role of excretory/secretory products (ESP) from C. sinensis in cell proliferation and the modulation of cancer related molecules, HEK293T cells were cultured with ESP and/or NDMA (N-nitrosodimethylamine), and then the mode of cell cycle and the expression of proteins were analyzed by using FACS, western blotting and confocal analysis. When the ESP of C. sinensis and NDMA were treated, the degree of cell proliferation was upregulated and the proportion of G2/M phase cells were increased by 25%-30% as compared with that of control. The expression pattern of the cell cycle proteins was also changed when both ESP and NDMA were added. Theses indicate that ESP from C. sinensis and NDMA synergistically affected the regulation of cell cycle proteins. In addition, the levels of Cox-2 and connexin 43 (Cx43) which is known as cancer related gap junction protein were upregulated by the addition of ESP and NDMA in vivo. In addition, the level of another gap junction protein, Cx32, which is also known as cancer inhibitor was down- regulated. Our results suggest that exposure to C. sinensis and a small amount of NDMA promote uncontrolled cellular proliferation of the bile duct epithelial cells and the upregulation of cancer related intracellular molecules.
- Copyright © 2013 by The American Association of Immunologists, Inc.