The Effects of Cannabidiol and Prognostic Role of TRPV2 in Human Endometrial Cancer

Oliviero Marinelli, Maria Beatrice Morelli, Daniela Annibali, Cristina Aguzzi, Laura Zeppa, Sandra Tuyaerts, Consuelo Amantini, Frédéric Amant, Benedetta Ferretti, Federica Maggi, Giorgio Santoni, Massimo Nabissi

International Journal of Molecular Sciences, 2020, 21, 5409

doi : 10.3390/ijms21155409

 

Abstract :

Several studies support, both in vitro and in vivo, the anti-cancer effects of cannabidiol (CBD), a transient receptor potential vanilloid 2 (TRPV2) ligand. TRPV2, often dysregulated in tumors, is associated with altered cell proliferation and aggressiveness. Endometrial cancer (EC) is historically divided in type I endometrioid EC and type II non-endometrioid EC, associated with poor prognosis. Treatment options with chemotherapy and combinations with radiation showed only limited ecacy. Since no data are reported concerning TRPV2 expression as well as CBD potential effects in EC, the aim of this study was to evaluate the expression of TRPV2 in biopsies and cell lines as well as the eects of CBD in in vitro models. Overall survival (OS), progression-free survival (PFS), cell viability, migration, and chemo-resistance have been evaluated. Results show that TRPV2 expression increased with the malignancy of the cancer tissue and correlated with shorter PFS (p = 0.0224). Moreover, in vitro TRPV2 over-expression in Ishikawa cell line increased migratory ability and response to cisplatin. CBD reduced cell viability, activating predominantly apoptosis in type I cells and autophagy in mixed type EC cells. The CBD improved chemotherapeutic drugs cytotoxic eects, enhanced by TRPV2 over-expression. Hence, TRPV2 could be considered as a marker for optimizing the therapy and CBD might be a useful therapeutic option as adjuvant therapy.

Keywords : cannabidiol; TRPV2; endometrial cancer; progression-free survival; migration; chemo-resistance

 

1. Introduction

Medical Cannabis (MC) and pure phyto-cannabinoids (as tetrahydrocannabinol, THC and cannabidiol, CBD) have been largely studied for their ability to ameliorate some of the most common and debilitating symptoms in cancer patients, like nausea, vomiting and pain [1,2].

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