Gastric Cancer
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 28, 2007; 13(48): 6498-6505
Published online Dec 28, 2007. doi: 10.3748/wjg.v13.i48.6498
Effect of arsenic trioxide on vascular endothelial cell proliferation and expression of vascular endothelial growth factor receptors Flt-1 and KDR in gastric cancer in nude mice
Yan-Feng Xiao, De-Dong Wu, Shan-Xi Liu, Xi Chen, Li-Fen Ren
Yan-Feng Xiao, De-Dong Wu, Xi Chen, Li-Fen Ren, Department of Pediatrics, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710049, Shaanxi Province, China
Shan-Xi Liu, Department of Hematology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710049, Shaanxi Province, China
Supported by The Science Fund of the Second Affiliated Hospital of the Medical College, No. 2003-YL-35
Correspondence to: Dr. Yan-Feng Xiao, Department of Pediatrics, The Second Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an 710049, Shaanxi Province, China. xiaoyanfeng0639@sina.com
Telephone: +86-29-87679541 Fax: +86-29-88494931
Received: June 29, 2007
Revised: September 5, 2007
Accepted: September 16, 2007
Published online: December 28, 2007
Abstract

AIM: To investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1) and VEGFR-2 (KDR) in human gastric tumor cells and proliferation of vascular endothelial cells.

METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were treated with As2O3. Microvessel density (MVD) and expression of Flt-1 and KDR were detected by immunofluorescence laser confocal microscopy. SGC-7901 cells were treated respectively by exogenous recombinant human VEGF165 or VEGF165 + As2O3. Cell viability was measured by MTT assay. Cell viability of ECV304 cells was measured by MTT assay, and cell cycle and apoptosis were analyzed using flow cytometry.

RESULTS: The tumor growth inhibition was 30.33% and 50.85%, respectively, in mice treated with As2O3 2.5 and 5 mg/kg. MVD was significantly lower in arsenic-treated mice than in the control group. The fluorescence intensity levels of Flt-1 and KDR were significantly less in the arsenic-treated mice than in the control group. VEGF165 may accelerate growth of SGC7901 cells, but As2O3 may disturb the stimulating effect of VEGF165. ECV304 cell growth was suppressed by 76.51%, 71.09% and 61.49% after 48 h treatment with As2O3 at 0.5, 2.5 and 5 μmol/L, respectively. Early apoptosis in the As2O3-treated mice was 2.88-5.1 times higher than that in the controls, and late apoptosis was 1.17-1.67 times higher than that in the controls.

CONCLUSION: Our results showed that As2O3 delays tumor growth, inhibits MVD, down-regulates Flt-1 and KDR expression, and disturbs the stimulating effect of VEGF165 on the growth of SGC7901 cells. These results suggest that As2O3 might delay growth of gastric tumors through inhibiting the paracrine and autocrine pathways of VEGF/VEGFRs.

Keywords: Arsenic trioxide; Gastric tumor; Flt-1; Tumor growth inhibition