Recombinant Snake Venom Cystatin Inhibits Tumor Angiogenesis in vitro and in vivo Associated with Downregulation

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 14, 10 Issues, 2014


Download PDF Flyer




Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 22nd of 58 in Chemistry, Medicinal
  • 85th of 202 in Oncology

Submit Abstracts Online Submit Manuscripts Online

Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 2.939
5 - Year: 3.37

Recombinant Snake Venom Cystatin Inhibits Tumor Angiogenesis in vitro and in vivo Associated with Downregulation

Author(s): Qun Xie, Nanhong Tang, Rong Wan, Yuanlin Qi, Xu Lin and Jianyin Lin


Abstract

Previous studies have shown that recombinant snake venom cystatin (sv-cystatin) inhibits the invasion and metastasis of tumor cells in vitro and in vivo. The purpose of this study was to investigate the ability of recombinant sv-cystatin to inhibit tumor angiogenesis in vitro and in vivo, and the mechanisms underlying this effect. Recombinant sv-cystatin inhibited proliferation of human umbilical vein endothelial cells (HUVECs) at 100 and 200 ?g/mL after 72, 96 and 120 h. Recombinant sv-cystatin also inhibited tumor–endothelial cell adhesion at 25, 50, 100 and 200 ?g/mL. Recombinant sv-cystatin inhibited capillary-like tube formation by HUVECs at 10, 25, 50, 100 and 200 ?g/mL following 12, 24 and 36 h incubation. Furthermore, recombinant sv-cystatin significantly suppressed microvessel density (MVD) of lung tumor colonies in C57BL/6 mice inoculated in the lateral tail vein with B16F10 melanoma cells. Administration of recombinant sv-cystatin significantly decreased MVD of primary tumor tissues in nude mice implanted subcutaneously with human hepatocellular carcinoma cells (MHCC97H). Exposure of B16F10 and MHCC97H cells to increasing doses of recombinant sv-cystatin suppressed secretion of vascular endothelial growth factor (VEGF)-A165 and basic fibroblast growth factor (bFGF) into the surrounding medium (P<0.05). The expression of fms-related tyrosine kinase 1 (Flt-1) protein in HUVECs was decreased by 25, 50, 100 and 200 ?g/mL recombinant sv-cystatin (P<0.05). This study demonstrates that recombinant sv-cystatin inhibits tumor angiogenesis associated with downregulation of VEGF-A165, Flt-1 and bFGF. This suggests that recombinant sv-cystatin may have potential pharmaceutical applications as an antiangiogenic and antimetastatic therapeutic agent.


Purchase Online Rights and Permissions

  
  



Article Details

Volume: 13
First Page:
Last Page:
Page Count:
DOI: 10.2174/1871520613666131125144802
Advertisement


Webmaster Contact: urooj@benthamscience.org Copyright © 2014 Bentham Science