| Background:Colon cancer is the third leading cause of cancer death in the western country and its incidences are increasing year by year in China, especially in the big cities. There were many studies have demonstrated that the rate of hepatic metastases in colon cancer was 15%～35% when the patients were found, and fairly high occurence of hepatic metastases has been observed in patients with colorectal cancer after radical operations. Epidemiological studies have documented a 40-50% reduction in the incidence of colon cancer in individuals taking nonsteroidal anti-inflammatory drugs drugs(NSAIDs). The reason relates to the inhibition of NSAIDs to cyclooxygenase(COX).COX is a membrane conjugated protein and is the rate-limiting enzyme in the synthesis of prostaglandins. Presently,it is known that human cell contains at least two forms of COX genes coding,COX-1 and COX-2. COX-2 is inducible immediate-early gene that is up-regulated by cytokines,growth factors,and mitogens. More and more studies have demonstrated that COX-2 expression is aberrantly increase in various human epithelial cancers,including those of colorectal,esophageal,lung,gastric,cervix and bladder origin,especially in colon cancer, there were some reports about COX-2 high expression combining with hepatic metastases in colon cancer.The growth and maintenance of solid tumors is angiogenesis dependent,including colorectal cancer, The growth of new blood vessels provides nutrients and a means of eliminating metabolic waste products by a process other than simple diffusion. The pioneer of angiogenesis research,Judah Folkman,has stated that" once tumor take has occurred,every increase in tumor cell population must be preceded by an increase in new capillaries converging on the tumor". Tumor is an avascular environment has slow linear growth,the size is limited in<2mm. After vascularization is becomes exponential. Tumor's angiogenesis not on1y provides nutrients but also provides the easy way to metastasis. Therefore angiogenesis play a important role in tumor growth and metastasis.It is believed that the balance of angiogenesis inducers and inhibitors governs the angiogenesis switch. The key finding in this field was the discovery of vascular endothelial growth factor(VEGF ),which is a highly potent angiogenic molecule specific for endothelial cells. Previous studies indicated that VEGF plays an important role in tumor angiogenesis in clinical human tumors,and that VEGF is a predictive factor for prognosis in colorectal cancer patients in association with metastatic potential. Studies suggest that many active material and several growth factors may be invovlved in the process of vascular structural remodeling. Basic fibroblast growth factor(bFGF) and nitric oxide(NO) are the two of them. FGF-2 can promote the proliferation and migration of vascular smooth cells and the growth of endothelial cells,increase the synthesis of elastin,and inhibit the cell apoptosis. And NO can inhibit proliferation of vascular smooth cells and relaxing them.lt can also promote apoptosis of vascular smooth cells and inhibit the synthesis of collagens,etc. They may play an important role in the process of sustained pulmonary hypertension in patients with CCP Therefore,more and more people focused on NO and bFGFObjective:To probe the effect of COX-2 on liver metastasis of human colonic cancer in nude mice through investing the correlation between COX-2 and angiogenesis factor, VEGF,FGF-2 and iNOS.Methods:1.Colon cancer cell strain, HT-29 and HCT-116 were grown in Dulbecco modified Eagle medium supplement 10% fetal calf serum and 100U/ml benzylpenicillin and 100U/ml streptomycin sulfate in a humidified atmosphere containing 5% of CO2 at 37℃2. To develop a colonic liver metastases model for experimental studies, BALB/c- nu/nu mice were selected to receive intiasplenic injectioci of 0.1ml solution containing 1×106 cells of colonic cells(HT-29 and HCT-116),The spleen was deleted.3. The expression of VEGF ,FGF-2,iNOS of cancer of colonic liver metastase...
|
PDF Full Text Request