摘要
Objective To study the inhibition effect on tumor angiogenesis and metastasis of angionstatin, which generated from human plasminogen. Methods Plasminogen was isolated metastasis of angio-from human plasma by Sepharose chromatography arm then catalyzed by elastase. Angiostatin was isolated by Sepharose 4B-Lysine chromatography. Nude mice model of metastatic gastric cancer was set up by intact tumor tissue implantation orthotopically. From the day of operation, mice received daily intraperitoneal injections of human angiostatin,intact plasminogen, or saline, respectively. 24μg ( 1.2mg/kg) of angiostatin or plasminogen was given on the day of operation, followed by a daily dose of 12μg( 0. 6mg /kg ) via intraperitoneal injection for three weeks.Ten weeks after implantation, mice were sacrificed and autopsied. Microvascular density was measured by im.munohistochemistry. Results Molecular weight of plasminogen isolated from plasma was 94KD. Plaanino-gen was catalyzed into two fragment peptides by elastase , which were 41～43KD and 51～53KD in molecular weight. Growth of the orthotopically implanted tumor was significantly reduced in size in the mice treated with angiostastin with an inhibition rate of 54.0%. Tumor metastasis to the liver and peritoneum was also signifi-cantly inhibited by angiostatin with inhibition rate of 61.9% and 55.6% respectively. The microvascular den-sity was also decreased significantly in the angiostatin treated mice. Conclusion Angiostatin may be generat-ed from plasma, and has inhibitory effect both on tumor growth and metastasis in nude mice model of human gastric cancer.
