Effect of non-anticoagulant N-desulfated heparin on expression of vascular endothelial growth factor, angiogenesis and metastasis of orthotopic implantation of human gastric carcinoma

Abstract

AIM:To investigate the effect of N-desulfated heparin on tumor metastasis and angiogenesis, and expression of vascular endothelial growth factor (VEGF) of orthotopic implantation of human gastric carcinoma in male severe combined immune deficiency (SCID) mice. METHODS:Human gastric cancer SGC-7901 cells were orthotopically implanted into the stomach of SCID mice. The mice were randomly divided into normal saline group and N-desulfated heparin group. One week after operation, the mice in N-desulfated heparin group received i.v. injections of N-desulfated heparin (Shanghai Institute of Cell Biology, Chinese Academy of Sciences, 10 mg/kg.d) twice weekly for 3 wk. The mice in normal saline group received i.v. injections of normal saline (100 μL) twice weekly for 3 wk. The mice were sacrificed six weeks after implantation. Tumor metastasis was evaluated histologically for metastasis under microscope. Intratumoral microvessel density (MVD) and VEGF expression were evaluated immuohistochemically. VEGF mRNA expression in gastric tissue of SCID mice was detected by real time PCR. RESULTS:The tumor metastasis rate was 80% in normal saline group and 20% in N-desulfated heparin group (P < 0.05). MVD was 8.0 ± 3.1 in normal saline group and 4.3 ± 1.8 in N-desulfated heparin group (P < 0.05). VEGF positive immunostaining was found in cytoplasm of cancer cells. The rate of VEGF positive expression was higher in normal saline group than in N-desulfated heparin treated group (90% vs 20%, P < 0.05). VEGF mRNA

Glycosaminoglycan mimicry by COAM reduces melanoma growth through chemokine induction and function

“…Heparin coupled to Sepharose has been widely used to purify chemokines 18. Because of its structural resemblance with COAM (polymeric and polyanionic nature) and the described antitumoral potency of heparin,19–23 it was evident to use heparin as a control polyanion for comparison with tumor growth inhibition by COAM. As shown in Figures 6 c and 6 d , 100 μg COAM was a significantly stronger antitumoral agent than 100 μg heparin.…”

RNAi‐mediated silencing of ezrin gene reverses malignant behavior of human gastric cancer cell line SGC‐7901

“…Gastric carcinomas are among the most prevalent malignancies as well as being the leading cause of cancer deaths in China. Up to the present, there have been no effective treatments for tumor metastasis 1,2 . Despite the new drugs and methods that have been developed in the treatment of gastric cancer, it remains a daunting clinical challenge.…”

“…Up to the present, there have been no effective treatments for tumor metastasis. 1,2 Despite the new drugs and methods that have been developed in the treatment of gastric cancer, it remains a daunting clinical challenge. Ezrin belongs to the ezrin/radixin/moesin protein family, which acts as membrane organizer and link between the plasma membrane and the cytoskeleton.…”

Urinary Metabolomic Analysis of Human Gastric Cancer Mouse Models and Patients Using Gas Chromatography/Mass Spectrometry

“…Each tumor piece was weighed and adjusted to be approximately 100 mg. All animals were randomly divided into three groups which included metastasis group (n=8), non-metastasis group (n=8), and normal group (n=7). Metastatic model was made using orthotopic implantation of histologically intact tissue of human gastric cancer [12]. Mice were anesthetized with 4.3% trichloraldehyde hydrate.…”