PAF receptor antagonist Ginkgolide B inhibits tumourigenesis and angiogenesis in colitis-associated cancer

Int J Clin Exp Pathol. 2015 Jan 1;8(1):432-40. eCollection 2015.

Abstract

Platelet activating factor (PAF), a potent pro-inflammatory phospholipid, has been found to trigger tumor growth and angiogenesis through its G-protein coupled receptor (PAFR). This study was aimed to investigate the potential role of PAF in azoxymethane (AOM)/dextran sulfate sodium (DSS) induced colitis-associated cancer (CAC), using PAFR antagonist Ginkgolide B (GKB). We found GKB up-regulated serum level of PAF-AH activity. As assessed by disease activity index (DAI), histological injury scores, leukocytes infiltration, and expression of pro-inflammatory cytokines, GKB ameliorated colonic inflammation and decreased tumor number and load in mice. GKB also decreased expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in tumor. These results suggest that PAFR antagonist might be a potential therapeutic strategy for CAC.

Keywords: Ginkgolide B; PAF; VEGF; angiogenesis; colitis-associated cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azoxymethane
  • Carcinogenesis / drug effects*
  • Carcinogenesis / pathology
  • Colitis / chemically induced
  • Colitis / pathology*
  • Dextran Sulfate
  • Female
  • Ginkgolides / pharmacology
  • Ginkgolides / therapeutic use*
  • Lactones / pharmacology
  • Lactones / therapeutic use*
  • Mice
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Platelet Activating Factor / antagonists & inhibitors*

Substances

  • Ginkgolides
  • Lactones
  • Plant Extracts
  • Platelet Activating Factor
  • Dextran Sulfate
  • ginkgolide B
  • Azoxymethane