Combined Endostatin Gene With Continuous Low-dose Cisplatin Inhibits Growth Of Pancreatic Carcinoma

Purpose : To investigate whether endostatin can inhibit the growth of pancreatic carcinoma and the peritoneal dissemination of pancreatic carcinoma and understand the possibility of antiangiogenic gene therapy with recombinant mouse endostatin adenovirus.Here we further investigate whether endostatin combines with continuous low-dose cisplatin can enhanced antitumor efficacy in the peritoneal dissemination of pancreatic carcinoma model. Methods: In the nude mouse model of pancreatic cancer, a total of 5×106 cells of Panc-1 were inoculated into the peritoneal cavity of the mude mice.The nude mouse were treated with intraperitoneal injection of 2×109pfu Ad-mEndo, NS, cisplatin or combined Ad-mEndo with low-dose cisplatin. Weekly intraperitoneal administration of Ad-mEndo was continued 4 times from day 2 before the implantation. Cisplatin at 0.2mg/kg was intraperitoneal administered once a day for a total of 5 times from 2 day after the implantation.We observed their antitumor effects,the serum levels of endostatin protein were measured by ELISA,the microvessel were measured by immunohistochemical analysis. Results:In this nude mouse model of pancreatic cancer, endostatin was expressed in the serum after intrapertoneal injection of Ad-Endostatin.In the study group,serum levels of endostatin in treated group were at the top in the third day after injection. The MVD of continuous low-dose cisplatin or adenovirus Ad-mEndo resulted in significant lower than that of the control group(NS),The MVD of group treated with combined Ad-mEndo and continuous low-dose cisplatin were much lower than has been observed with any any agent alone(p<0.01).Combined Ad-mEndo and continuous low-dose cisplatin or treatment with adenovirus Ad-mEndo resulted in significant the growth inhibition of peritoneal dissemination of pancreatic carcinoma compared with the control group(NS) (p<0.01,p<0.05). Combined Ad-mEndo and continuous low-dose cisplatin in more effective growth inhibition of peritoneal dissemination of pancreatic carcinoma than has been observed with any agent alone(p<0.01,p<0.05). Conclusions: These result provide evidence that treatment with endostatin gene efficiently suppresses tumor angiogenesis, and inhibites the growth of peritoneal dissemination of pancreatic carcinoma, and combined endostatin with continuous low-dose cisplatin obtains an enhanced inhibition of pancreatic tumor growth, our data suggested that endostatin in combination with continuous low-dose cisplatin may provide a new combined therapy approach for human pancreatic cancer in clinic.