A novel insight into the anticancer mechanism of metformin in pancreatic neuroendocrine tumor cells

E. Vitali, I. Boemi, S. Piccini, G. Tarantola, V. Smiroldo, E. Lavezzi, T. Brambilla, A. Zerbi, C. Carnaghi, G. Mantovani, A. Spada, A. G. Lania

Research output: Contribution to journalArticlepeer-review


The antidiabetic drug metformin displays anticancer properties in several neoplasms. In pituitary NETs, aryl hydrocarbon receptor-interacting protein (AIP) is up-regulated by the somatostatin analog octreotide. Metformin inhibited QGP-1 cell proliferation in a dose- and time-dependent manner, at concentrations similar to those achievable in treated patients (−31 ± 12%, p < 0.05 vs basal at 100 μM). Moreover, metformin decreased pancreatic neuroendocrine tumors (PAN-NETs) cell proliferation (−62 ± 15%, p < 0.0001 vs basal at 10 mM), without any additive effect when combined with octreotide. Both octreotide and metformin induced AIP up-regulation. AIP silencing abolished the reduction of mTOR phosphorylation induced by metformin and octreotide. Moreover, metformin decreased HSP70, increased Zac1 and AhR expression; these effects were abolished in AIP silenced QGP-1 cells. In conclusion, metformin acts as an anticancer agent in PAN-NET cells, its activity is mediated by AIP and its interacting proteins. These findings provide a novel insight into the antitumorigenic mechanism of metformin.

Original languageEnglish
Article number110803
JournalMolecular and Cellular Endocrinology
Publication statusPublished - Jun 1 2020


  • AIP
  • Metformin
  • mTOR
  • Octreotide
  • Pancreatic neuroendocrine tumors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology


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