Abstract
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.
Highlights
Gastric cancer is the common alimentary tract cancer in China in terms of incidence
We investigated the effect of N-desulfated heparin on basic fibroblast growth factor (bFGF) expression, angiogenesis, and tumor metastasis in vitro and in vivo
The metastatic rate was higher in mice treated with normal saline than in those treated with Ndesulfated heparin (90% versus 20%, P < 0.05)
Summary
Gastric cancer is the common alimentary tract cancer in China in terms of incidence. It is one of the malignancies that do serious harm to people’s health with a high mortality and are short of effective therapeutic methods. Recent studies have showed that angiogenesis plays a crucial role in tumor growth and metastasis. Vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) are the main factors promoting angiogenesis [7, 8]. Anti-VEGF therapy is effective in inhibiting angiogenesis and metastasis of tumor [9, 10]. Aside from its anticoagulant action, heparin binds to various growth factors, cytokines, and extracellular proteins and is able to affect migration of cancer cells and angiogenesis in tumors. Modified heparin shows a significantly reduced anticoagulant activity and enhanced ability to interact with FGF, VEGF, and hepatocyte growth factor, which are known to stimulate angiogenesis [13]. We investigated the effect of N-desulfated heparin on bFGF expression, angiogenesis, and tumor metastasis in vitro and in vivo
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