Effect of Non-Anticoagulant N-Desulfated Heparin on Basic Fibroblast Growth Factor Expression, Angiogenesis, and Metastasis of Gastric Carcinoma In Vitro and In Vivo

Objective. The present study was performed to investigate the effect of N-desulfated heparin on basic fibroblast growth factor (bFGF) expression, tumor angiogenesis and metastasis of gastric carcinoma. Methods. Human gastric cancer SGC-7901 tissues were orthotopically implanted into the stomach of NOD SCID mice. Twenty mice were randomly divided into two groups which received either intravenous injection of 0.9% NaCl solution (normal saline group) or 10 mg/kg N-desulfated heparin (N-desulfated heparin group) twice weekly for three weeks. In vitro, human gastric carcinoma SGC-7901 cells were treated with N-desulfated heparin in different concentration (0.1 mg/mL, 1 mg/mL, N-desulfated heparin group), and treated with medium (control group). Results. In vivo, the tumor metastasis rates were 9/10 in normal saline group and 2/10 in N-desulfated heparin group (P < 0.05). The intratumoral microvessel density was higher in normal saline group than in N-desulfated heparin group (P < 0.05). bFGF expression in gastric tissue was inhibited by N-desulfated heparin (P < 0.05). There was no bleeding in N-desulfated heparin group. In vitro, N-desulfated heparin inhibited significantly bFGF protein and mRNA expression of gastric carcinoma cells (P < 0.05). Conclusions. N-desulfated heparin can inhibit the metastasis of gastric cancer through inhibiting tumor bFGF expression and tumor angiogenesis with no obvious anticoagulant activity.