TRPV2 correlates with endometrial cancer aggressiveness and its activation by cannabidiol induces cytotoxicity and improves chemosensitivity

Introduction: Endometrial cancer (EC) is the most diagnosed gynaecological malignancy in developed countries and comprises type I endometrioid EC and type II non-endometrioid EC, the most aggressive and with poor prognosis [1]. Treatment options have limited efficacy, mainly in relapsed or metastasized EC. Transient Receptor Potential Vanilloid 2 (TRPV2) has been asso- ciated with altered tumour cell proliferation, invasiveness, and aggressiveness, in fact is often dysregulated in tumours [2]. Cannabidiol (CBD), is considered a TRPV2 agonist, and was stud- ied for its anti-tumoral effects in many human cancer models [3]. Aims: TRPV2 expression in EC biopsies and EC cell lines and the effect of CBD-induced TRPV2 activation in EC cell line models. Methods: Evaluation of TRPV2 expression in EC cell lines by RT-PCR and western blot and in EC biopsies by immunohisto- chemistry. Analysis of TRPV2 correlation with Overall Survival (OS) and Progression-Free Survival (PFS) by Kaplan–Meier analy- sis. TRPV2 transfection and CBD-induced activation to evaluate the effects on cytotoxicity, migration, and chemosensitivity, by cell viability, wound healing, gene and protein expression profiles analysis. Results: Results show that EC malignancy correlates with high expression of TRPV2, that is associated with shorter PFS. TRPV2 transfection increased migration, Akt phosphorylation and improved response to cisplatin. CBD induced cell death, mainly by apoptosis in type I cells and autophagic-cell death in mixed type EC cells. CBD improved chemosensitivity, with higher efficacy in TRPV2 over-expressing EC cell lines. Conclusions: Data evidence that TRPV2 expression increases EC aggressiveness, suggesting its potential use as diagnostic marker in EC. Moreover, seen the effect of CBD on EC cell lines, these data suggested its potential use, in a promising strategy, as adjuvant therapeutical drug.