A framework for the in vitro evaluation of cancer-relevant molecular characteristics and mitogenic potency of insulin analogues

Research output: Contribution to journalArticle

  • External authors:
  • Ivona Baricevic-Jones
  • David R Jones (Collaborator)
  • Anne Lutzen (Collaborator)
  • A Lundby (Collaborator)
  • J Worm (Collaborator)
  • Bo F Hansen (Collaborator)

Abstract

Epidemiological and laboratory studies raise the possibility of a link between clinically prescribed insulin analogues and increased cancer risk. Accordingly, there is a regulatory mandate for cancer-related pre-clinical safety evaluation during insulin analogue development, but currently, there is no standardized framework for such in vitro evaluation. We tested human insulin; the super-mitogenic insulin, X10 and insulin-like growth factor I, in four cancer cell lines with a range of insulin-like growth factor-I receptor (IGF-IR)/IR (insulin receptor) ratios (HCT 116, HT-29, COLO 205 and MCF7) and related these to IGF-IR and IR expression in 17 human adenocarcinomas. All cell types were IR-A isoform dominant. We determined IGF-IR/IR signalling pathway endpoints in dose- and time-varying experiments, and performed mitogenic dose-response equivalent assays to derive EC50 values, and correlated these with IGF-IR/IR ratios. We superimposed relative EC50 values onto data from the literature in a meta-analysis. The IGF-IR/IR ratios varied from

Bibliographical metadata

Original languageEnglish
Pages (from-to)1040-50
Number of pages989
JournalCarcinogenesis
Volume36
Issue number9
DOIs
Publication statusPublished - 30 May 2015