Agonist activation of estrogen receptor beta (ERβ) sensitizes malignant pleural mesothelioma cells to cisplatin cytotoxicity

Giulia Pinton, Arcangela G. Manente, Antonio Daga, Michele Cilli, Maurizio Rinaldi, Stefan Nilsson, Laura Moro

Research output: Contribution to journalArticle

Abstract

Background: Estrogen receptor (ER) β acts as a tumor suppressor in malignant mesotheliomas.Methods: Here we explored the anti-proliferative and anti-tumorigenic efficacy of the selective ERβ agonist, KB9520, in human mesothelioma cell lines in vitro and in a mesothelioma mouse model in vivo.Results: KB9520 showed significant anti-proliferative effect in ERβ positive human malignant pleural mesothelioma cells in vitro. Selective activation of ERβ with KB9520 sensitized the cells to treatment with cisplatin, resulting in enhanced growth inhibition and increased apoptosis. Furthermore, in CD1 nude mice mesothelioma tumor growth was significantly inhibited when KB9520 was added on top of the standard of care chemo combination cisplatin/pemetrexed, as compared to the cisplatin/pemetrexed alone group. Importantly, KB9520 exerted a protective effect to cisplatin toxicity in the non-malignant mesothelium derived MET5A cells.Conclusions: Together, the data presented suggest that selective targeting of ERβ may be an efficacious stand-alone treatment option and/or become an important add-on to existing malignant mesothelioma therapy.

Original languageEnglish
Article number227
JournalMolecular Cancer
Volume13
Issue number1
DOIs
Publication statusPublished - Oct 2 2014

Keywords

  • Cisplatin
  • Estrogen Receptor β
  • Malignant mesothelioma
  • Receptor agonist
  • Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

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