Dr. PL Cui and Dr. MH Yu contributed equally to this work.
Melatonin prevents human pancreatic carcinoma cell PANC-1-induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression
Version of Record online: 14 SEP 2011
© 2011 John Wiley & Sons A/S
Journal of Pineal Research
Volume 52, Issue 2, pages 236–243, March 2012
How to Cite
Cui, P., Yu, M., Peng, X., Dong, L. and Yang, Z. (2012), Melatonin prevents human pancreatic carcinoma cell PANC-1-induced human umbilical vein endothelial cell proliferation and migration by inhibiting vascular endothelial growth factor expression. Journal of Pineal Research, 52: 236–243. doi: 10.1111/j.1600-079X.2011.00933.x
- Issue online: 6 FEB 2012
- Version of Record online: 14 SEP 2011
- Accepted manuscript online: 11 AUG 2011 07:30PM EST
- Received June 9, 2011; Accepted August 8, 2011.
- human umbilical vascular endothelial cells;
- pancreatic carcinoma;
- vascular endothelial growth factor
Abstract: Melatonin is an important natural oncostatic agent, and our previous studies have found its inhibitory action on tumor angiogenesis, but the mechanism remains unclear. It is well known that vascular endothelial growth factor (VEGF) plays key roles in tumor angiogenesis and has become an important target for antitumor therapy. Pancreatic cancer is a representative of the most highly vascularized and angiogenic solid tumors, which responds poorly to chemotherapy and radiation. Thus, seeking new treatment strategies targeting which have anti-angiogenic capability is urgent in clinical practice. In this study, a co-culture system between human umbilical vein endothelial cells (HUVECs) and pancreatic carcinoma cells (PANC-1) was used to investigate the direct effect of melatonin on the tumor angiogenesis and its possible action on VEGF expression. We found HUVECs exhibited an increased cell proliferation and cell migration when co-cultured with PANC-1 cells, but the process was prevented when melatonin added to the incubation medium. Melatonin at concentrations of 1 μm and 1 mm inhibited the cell proliferation and migration of HUVECs and also decreased both the VEGF protein secreted to the cultured medium and the protein produced by the PANC-1 cells. In addition, the VEGF mRNA expression was also down-regulated by melatonin. Taken together, our present study shows that melatonin at pharmacological concentrations inhibited the elevated cell proliferation and cell migration of HUVECs stimulated by co-culturing them with PANC-1 cells; this was associated with a suppression of VEGF expression in PANC-1 cells.