Antineoplastic effect of WIN 55,212-2, a cannabinoid agonist, in a murine xenograft model of gastric cancer

Chemotherapy. 2013;59(3):200-6. doi: 10.1159/000355666. Epub 2013 Dec 3.

Abstract

Background: We have previously reported the antineoplastic effects of a cannabinoid agonist in gastric cancer cells. Our aim was to evaluate this in a murine xenograft model.

Methods: Animal models were created after injecting AGS gastric cancer cells subcutaneously into the flank of male BALB/c-nude mice. A cannabinoid agonist, WIN 55,212-2 (7 mg/kg body weight) or vehicle was injected around the tumor subcutaneously every 24 h for 14 days. Tumors were explanted for analysis.

Results: Tumor volume decreased by 30% in the WIN 55,212-2-treated group compared to the group treated with vehicle (p < 0.05). Apoptotic cells were found more commonly in the WIN 55,212-2 treatment group than in the control on immunohistochemistry. Compared to the control, WIN 55,212-2 treatment significantly increased caspase-3 cleavage and decreased MMP-2, MMP-7 and MMP-9 protein levels significantly (all p < 0.05). VEGF-A protein level was not different between the 2 groups.

Conclusion: WIN 55,212-2 has antineoplastic effect on the gastric cancers in in vivo model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Benzoxazines / pharmacology*
  • Benzoxazines / therapeutic use*
  • Cannabinoid Receptor Agonists / pharmacology*
  • Cannabinoid Receptor Agonists / therapeutic use*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Humans
  • Male
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Morpholines / pharmacology*
  • Morpholines / therapeutic use*
  • Naphthalenes / pharmacology*
  • Naphthalenes / therapeutic use*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Transplantation, Heterologous
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antineoplastic Agents
  • Benzoxazines
  • Cannabinoid Receptor Agonists
  • Morpholines
  • Naphthalenes
  • Vascular Endothelial Growth Factor A
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Caspase 3
  • Matrix Metalloproteinases