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

International Journal of Molecular Sciences

Federica Maggi¹  Daniela Annibali²  Sandra Tuyaerts²  Frédéric Amant²  Benedetta Ferretti³  Consuelo Amantini⁴  Maria Beatrice Morelli⁵  Cristina Aguzzi⁵  Oliviero Marinelli⁵  Laura Zeppa⁵  Massimo Nabissi⁵  Giorgio Santoni⁵ 

[1] Department of Molecular Medicine, Sapienza University, 00155 Rome, Italy;Gynecological Oncology Department LKI, Leuven Cancer Institute KU, Leuven-University of Leuven, 3000 Leuven, Belgium;Oncologia Medica, Ospedale di San Severino, 62027 San Severino Marche (MC), Italy;School of Bioscience and Veterinary Medicine, University of Camerino, 62032 Camerino (MC), Italy;School of Pharmacy, University of Camerino, 62032 Camerino (MC), Italy;

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

DOI  :  10.3390/ijms21155409

来源: DOAJ

【 摘 要 】

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 efficacy. 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 effects 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 effects, 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.

【 授权许可】

Unknown