COX-2 Regulates HIF-1α And VEGF Expression In Human Pancreatic Carcinoma

Background:Pancreatic cancer is one of the solid and malignant tumors in human body. In recent years, the incidence of pancreatic cancer has been increasing. With a high invasive ability and low rate of early diagnosis and suigical resection, pancreatic cancer has a poor prognosis.5-years survival rate is less than 5%. So far, how to diagnose and therapy earlier remains difficult all over the world. Surgery is the only way to cure pancreatic cancer. In term of the extention of cancer after diagnosis, less than 10% patients were appropriate for surgery. With some certain complications, patients who accept surgery had poor survival quality. Long-term clinical practices have indicated that surgery alone has limited value in the treatment of pancreatic cancer. In recent years, most expert and doctor develop such a opinion that combined therapy consisting of surgery,chemotherapy,radiotherapy and biotherapy is the primary management for pancreatic cancer. Currently available chemotherapeutic options for pancreatic cancer are also not very effective mainly due to the emergence of drug resistance. Accordingly, to improve the overall survival of patients with pancreatic cancer, there is an urgent need to develop effective treatment for this disease, such as new chemotherapeutic agents, interventional therapy and gene therapy. The key of improving therapeutic efficacy is to expand the understanding of etiopathogenesis and molecular/genetic biology of pancreatic cancers, which should facilitate research to develop novel molecular-targeted agents and new herapeutic approachs for this disease. Objectives:Detecting the cyclooxygenase-2 (COX-2),hypoxia inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) protein expression in pancreatic carcinoma tissues. Then the effect of COX-2-selected inhibitor nimesulide with different concentration on the expression of COX-2,HIF-la and VEGF in human pancreatic cell line BxPC-3 cells was observed. Furthermore, the relationship of COX-2 expression and tumor angiogenesis was analyzed.Methods:The protein expression of COX-2,HIF-la and VEGF in 12 cases of pancreatic cancer and corresponding paracarninoma tissues were detected by western blotting respectively. The effect of nimesulide with different concentration on COX-2,HIF-la and VEGF expression was also examined by western blotting.Results:There were significantly high levels of COX-2,HIF-la and VEGF expression in pancreatic carcinoma tissues compared with paracarninoma tissues. Furthermore, nimesulide with different concentration reduced the expression of three factors obviously, and there was a statistically significant difference on protein levels.ConclusionsOver-expression of COX-2 may be responsible for the increasing HIF-la and VEGF production in pancreatic carcinoma, which implicated that COX-2 may be related with tumor angiogenesis. Meanwhile, COX-2-selected inhibitor nimesulide could inhibit expression of HIF-la and VEGF protein in pancreatic carcinoma BxPC-3 cells induced by hypoxia, which may reveal one of its antiangiogenesis mechanisms.