Experimental Studies On The Inhibition Of Pancreatic Cancer By Antisense Heparanase Gene

OBJECTIVES:Pancreatic cancer, having highly aggressive biological behaviour, being prone to metastases at early stage and less than 5 % of 5-year survival rates after surgical intervention, is one of the worst poor prognosis tumors of malignant gastrointestinal tract. Local invasion and metastases of tumor is the principal reason to affect the effect of surgical treatment and overall survival time. Though great advance was developed of the therapy mode in pancreatic cancer, the general treatment effect was unsatisfactory. Identification of invasion and metastases related genes of pancreatic cancer and dissection of the mechanism of it at molecular level is key conditions to improve the treatment effect of this disease. In recent years, considerable research focusing on the mechanism of carcinogenesis, especial on metastasis in pancreatic cancer became hotspot in this field. Heparanase gene, cloned and identified to be tumor related gene in recent years, plays an important role in the process of invasion and metastases of malignant tumor. Heparanase, an endoglycosidase specifically recognizing the chief components of extracellular matrix and cleaving the heparan sulfate chain of heparan sulfate proteoglycans, degrading the barrier structure comprising of extracellular matrix and basement membranes, is involved in angiogenesis and contributes to tumor invasion and metastases. Previous studies show that heparanase gene is related to invasion, metastases and prognosis of patients in a variety of malignancies. Thereby it might act as a common tumor-specific antigen and a promising good target of gene-therapy application for human most of tumors. The development of tumor related genes targeted therapy provides a potential novel way to treat pancreatic cancer. The techinque of antisense gene targeting invasion, metastases related genes of pancreatic cancer maybe a good approach to treat this disease. Up to date there still has been not the basic research on antisense heparanase gene for gene therapy in pancreatic cancer. In the present study, we constructed the green fluorescent protein (GFP) eukaryotic co-expressing vectors with sense or antisense heparanase gene recombinatants and transfected pancreatic cancer cell line SVV1990. Furthermore, the inhibitory effect of antisense heparanase gene on tumor invasion, metastases and angiogenesis were...