Antitumorigenic and antiinsulinogenic effects of calcitriol on insulinoma cells and solid β-cell tumors

Francesca Galbiati, Luca Polastri, Silvia Gregori, Massimo Freschi, Mara Casorati, U. G.O. Cavallaro, Paolo Fiorina, Federico Bertuzzi, Alessandro Zerbi, Guido Pozza, Luciano Adorini, Franco Folli, Gerhard Christofori, Alberto M. Davalli

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Malignant insulinoma is a rare form of cancer with a poor prognosis because of metastatic dissemination and untreatable hypoglycemia. Effective chemotherapy of patients who are not cured by surgery is needed. Calcitriol has known anticancer properties on different neoplastic cell lines, but no data are available regarding its activity on tumorigenic pancreatic β-cells. We analyzed the in vitro effects of calcitriol on the murine insulinoma cell line βTC3 and primary cultures of human isolated islets and benign insulinoma. The effect of in vivo calcitriol administration on insulinoma of recombinant insulin/Simian virus 40 oncogene-expressing transgenic mice was also investigated. In βTC3, calcitriol induced growth inhibition; apoptosis; down-regulation of insulin gene expression; and nongenomic activation of the MAPK pathway. MAPK kinase inhibitor (UO126) and staurosporine reduced calcitriol-mediated βTC3 death, and down-regulation of insulin gene transcription was prevented by staurosporine but not UO126. Calcitriol significantly decreased insulin release and mRNA levels of human islets and insulinoma cells. Finally, recombinant insulin/Simian virus 40 oncogene-expressing transgenic mice treated with calcitriol showed reduced insulinoma volumes because of increased apoptosis of adenomatous cells. Together, these findings provide the rationale for testing the efficacy of calcitriol in the treatment of patients with solid β-cell tumors.

Original languageEnglish (US)
Pages (from-to)4018-4030
Number of pages13
JournalEndocrinology
Volume143
Issue number10
DOIs
StatePublished - Oct 1 2002

ASJC Scopus subject areas

  • Endocrinology

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