TY - JOUR
T1 - The effects of cannabidiol and prognostic role of TRPV2 in human endometrial cancer
AU - Marinelli, Oliviero
AU - Morelli, Maria Beatrice
AU - Annibali, Daniela
AU - Aguzzi, Cristina
AU - Zeppa, Laura
AU - Tuyaerts, Sandra
AU - Amantini, Consuelo
AU - Amant, Frédéric
AU - Ferretti, Benedetta
AU - Maggi, Federica
AU - Santoni, Giorgio
AU - Nabissi, Massimo
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - Cannabidiol
KW - Chemo-resistance
KW - Endometrial cancer
KW - Migration
KW - Progression-free survival
KW - TRPV2
UR - http://www.scopus.com/inward/record.url?scp=85088938547&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms21155409
DO - https://doi.org/10.3390/ijms21155409
M3 - Article
C2 - 32751388
SN - 1661-6596
VL - 21
SP - 1
EP - 23
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 15
M1 - 5409
ER -