ECE2017 Eposter Presentations: Interdisciplinary Endocrinology Endocrine tumours and neoplasia (9 abstracts)
Potential role of vitamin D in restoring sensitivity to mTOR inhibitors in hepatocellular carcinoma (HCC): 1,25(OH)vitamin D (VitD) reverts everolimus (EVE) resistance in a hcc cell line
Claudia Pivonello 1 , Donatella Paola Provvisiero 1 , Mariarosaria Negri 1 , Gilda Di Gennaro 1 , Cristina de Angelis 2 , Chiara Simeoli 1 , Giacomo Galdiero 1 , Maria Cristina De Martino 1 , Annamaria Colao 1 & Rosario Pivonello 1
1Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy; 2I.O.S. and COLEMAN S.r.l., Naples, Italy.
HCC is a difficult-to-treat- cancer with poor prognosis. Despite EVOLVE-1 trial demonstrated that EVE did not improve overall survival in molecularly and clinically unselected patients with advanced sorafenib resistant HCC, in selected patients, the established antitumor effect of EVE could make this drug a potential adjuvant therapy. Unfortunately, the acquired EVE resistance due to the tumour adaptation to chronic drug use is a current challenge. VitD has been deemed as potential regimen to treat a variety of cancers alone or in combination with other drugs. The aim of this study was to assess the antiproliferative effect of the combined treatment with EVE and VitD in JHH-6, a model of HCC cell line, and to explore the role of VitD pre-treatment in the re-sensitization to EVE in JHH-6 cell line resistant to EVE (JHH-6 EveR). JHH-6 EveR were obtained after 4 months of EVE 10-8M treatment. Messenger and protein VitD receptor (VDR) expression was confirmed by RT-qPCR and immunofluorescence. DNA assay was established to evaluate the proliferation rate in parental and EveR cells after EVE treatment (from 10–14 M to 10–8 M) alone or in combination with VitD (10–7 M). In parental cells, EVE significantly reduced the proliferation index in a dose-dependent manner after 6 days of treatment and VitD did not improve EVE effect. JHH-6 EveR cells no longer responded to EVE treatment but 12h and 24h of VitD pre-treatment was sufficient to significantly restore the efficacy of EVE at concentration ranging from 10–14 M to 10–8 M with a maximum effect of 3.3% at 10–8 M (P<0.001). Moreover, the liver miRNA PCR Array study demonstrated that VitD treated JHH-6 EveR showed an increased expression of miR-375 compared to JHH-6 EveR, suggesting a role of miR-375 in EVE re-sensitization. These preliminary data suggested the use of VitD to overcome the acquired resistance to EVE in HCC.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more