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, Frederic Amant, Benedetta Ferretti, Federica Maggi, Giorgio Santoni, Massimo Nabissi

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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 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.

Original languageEnglish
Article number5409
JournalInternational Journal of Molecular Sciences
Volume21
Issue number15
DOIs
Publication statusPublished - 29 Jul 2020

Bibliographical note

Funding Information:
This work was supported by grants from Enecta; M.B.M. was supported by Fondazione Umberto Veronesi (Post-doctoral Fellowship 2018, 2019) and O.M. from UNICAM School of Advanced Studies in Life and Health Sciences. Acknowledgments: Thanks to Dario Conti for his support on endometrial cancer research in UNICAM. F.A. was a senior researcher for Research Foundation—Flanders (FWO). S.T. was financially supported by the Anticancer Fund (www.anticancerfund.org) and by the associated Verelst Uterine Cancer Fund, Leuven.

Funding Information:
Acknowledgments: Thanks to Dario Conti for his support on endometrial cancer research in UNICAM. F.A. was a senior researcher for Research Foundation—Flanders (FWO). S.T. was financially supported by the Anticancer Fund (www.anticancerfund.org) and by the associated Verelst Uterine Cancer Fund, Leuven.

Funding Information:
Funding: This work was supported by grants from Enecta; M.B.M. was supported by Fondazione Umberto Veronesi (Post-doctoral Fellowship 2018, 2019) and O.M. from UNICAM School of Advanced Studies in Life and Health Sciences.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • cannabidiol
  • TRPV2
  • endometrial cancer
  • progression-free survival
  • migration
  • chemo-resistance

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