Metformin and Everolimus: A Promising Combination for Neuroendocrine Tumors Treatment.
everolimus
metformin
neuroendocrine tumors
resistance
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
02 Aug 2020
02 Aug 2020
Historique:
received:
13
07
2020
revised:
29
07
2020
accepted:
31
07
2020
entrez:
5
8
2020
pubmed:
5
8
2020
medline:
5
8
2020
Statut:
epublish
Résumé
Treatment options for neuroendocrine tumors (NETs) are rarely curative, as NETs frequently show resistance to medical therapy. The use of everolimus, an mTOR inhibitor, is limited by the development of resistance, probably due to the activation of Akt signaling. In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination. We investigated the effects of the metformin and everolimus combination on NET cell proliferation, apoptosis, colony formation, cell viability, NET spheroids growth and the involvement of the Akt and mTOR pathways, and also developed everolimus-resistant NET cells to further study this combination. Metformin and everolimus in combination are more effective than monotherapy in inhibiting pancreatic NET (PAN-NET) cell proliferation (-71% ± 13%, Considering the promising effects of the everolimus and metformin combination in NET cells, our results provide a rationale for its use in NET patients.
Identifiants
pubmed: 32748870
pii: cancers12082143
doi: 10.3390/cancers12082143
pmc: PMC7464161
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : 2017Z3N3YC
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