Antineoplastic Effect of WIN 55,212-2, a Cannabinoid Agonist, in a Murine Xenograft Model of Gastric Cancer

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.

WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals

“…Previous studies have shown the crucial role of WIN in tumor cell proliferation, apoptosis, and migration [13][14][15]. In the present study, we further determined the effects of WIN on the migration and invasion of GC cells.…”

“…WIN 55,212-2 (WIN), a cannabinoid agonist, inhibits cell proliferation by cell cycle arrest, inhibits cell invasion by downregulation of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor A (VEGF-A), and induces apoptosis by downregulation of phospho-AKT in gastric cancer cells [13,14]. In a murine xenograft model of gastric cancer, WIN reduced tumor growth via inducing tumor cell apoptosis [15]. A previous study showed a correlation between WIN and the metastasis of GC [13]; however, the mechanism remains unknown.…”

Targeting cannabinoid receptors in gastrointestinal cancers for therapeutic uses: current status and future perspectives

“…Consistent with a protective effect against gastrointestinal cancers, the cannabinoid receptor agonist WIN 55,212-2 has been shown to exert antineoplastic actions on the xenograft model of gastric cancer [16].…”

Synergistic interaction of the cannabinoid and death receptor systems – a potential target for future cancer therapies?

“…These drugs can increase appetite, reduce pain, and reduce chemotherapy‐associated nausea and vomiting. Many in vitro and in vivo studies also indicate that cannabinoid drugs can reduce tumor volume and induce cancer cell death . Both the CB1 and CB2 receptors, their endogenous ligands, and regulatory proteins are expressed, functionally active, and generally up‐regulated in most tumor cell lines .…”