Abstract 5878: Effect of cannabinoid WIN 55,212-2 on prostate cancer cell proliferation, migration, invasion, and tumor growth

Abstract

Abstract Introduction and Objective: Prostate cancer (PCa) is the most commonly diagnosed cancer in men and the second leading cause of cancer related death in Canada. A large body of evidence supports a possible role for cannabinoids in certain aspects of human health and disease, acting as palliative agents and more importantly, as inhibitors of cancer cell proliferation, migration, invasion, and the angiogenesis of tumours. WIN 55,212-2 (WIN) is a highly potent synthetic cannabinoid, binding to the cannabinoid receptors 1 and 2. This study aims to determine the anti-cancer effect of WIN using preclinical models of prostate cancer. Methodology: Human PCa cells (DU145, PC3) were treated with WIN at concentrations ranging from 1μM to 20μM and growth of cells (using the MTS assay) was assessed at various times following treatment. Wound-healing assays were conducted to investigate the migratory potential of cells following exposure to treatment, and trans-well invasion assays were performed to explore the influence of WIN on cell invasion. In vivo evaluation using PC3 xenografts was performed using swiss athymic mice. Treatment was administered thrice weekly and tumor volume assessed for a total of three weeks. Results: Treatment with 10μM WIN resulted in a significant reduction in the proliferation of DU145 and PC3 cells after 24 h compared to control (p<0.05). Cell migration and invasion studies revealed a significant reduction in cell motility at 15μM WIN (p<0.05) and a significant reduction in cell invasion at a concentration as low as 1μM (p<0.05). Treatment with 5mg/kg WIN (ip) revealed significant differences in tumor volume compared to controls that received the vehicle (p<0.05). There were no significant alterations in body weight in both groups. Conclusion: WIN 55,212-2 is a highly potent cannabinoid, having significant influences on cell proliferation, migration, and invasion, with reduction in the growth of tumors in prostate cancer xenografts. We are the first to demonstrate the use of WIN in PC3 xenografts and provide evidence for its use as a novel therapeutic option in patients with prostate cancer. Funding/Conflicts of Interest: None Citation Format: Domenica Roberto, Laurence H. Klotz, Vasundara Venkateswaran. Effect of cannabinoid WIN 55,212-2 on prostate cancer cell proliferation, migration, invasion, and tumor growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5878.