The role of GSK3 and its reversal with GSK3 antagonism in everolimus resistance.

ABSTRACT: Pancreatic neuroendocrine tumors (panNETs) are often inoperable at diagnosis. The mTORC1 inhibitor everolimus has been approved for the treatment of advanced NETs. However, the regular development of resistance to everolimus limits its clinical efficacy. We established two independent everolimus-resistant panNET (BON1) cell lines (BON1 RR1, BON1 RR2) to find potential mechanisms of resistance. After 24 weeks of permanent exposure to 10 nM everolimus, BON1 RR1 and BON1 RR2 showed stable resistance with cellular survival rates of 96.70% (IC₅₀ = 5200 nM) and 92.30% (IC₅₀ = 2500 nM), respectively. The control cell line showed sensitivity to 10 nM everolimus with cellular survival declining to 54.70% (IC₅₀ = 34 nM). Both resistant cell lines did not regain sensi

SUBMITTER: Aristizabal Prada ET 

PROVIDER: S-EPMC7439002 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature