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

SUMMARY OF THE RESEARCH PROJECT
FUNDED BY THE BUZZI UNICEM FOUNDATION
PROJECT LEADER:
Laura Moro (PhD)

SITE:
University of Eastern Piedmont “Amedeo Avogadro”

PROJECT STATUS:
Published in: Mol Cancer. 2014 Oct 2;13(1):227. [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/25277603

RESEARCH SUMMARY:
BACKGROUND: 
Estrogen receptor (ER) beta acts as a tumor suppressor in malignant mesotheliomas.

METHODS: 
Here we explored the anti-proliferative and anti-tumorigenic efficacy of the selective ERbeta agonist, KB9520, in human mesothelioma cell lines in vitro and in the mesothelioma mouse model in vivo.

RESULTS:
KB9520 showed significant anti-proliferative effect in ERbeta positive human malignant pleural mesothelioma cells in vitro. Selective activation of ERbeta 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 ERbeta may be an efficacious stand-alone treatment option and/or become an important add-on to existing malignant mesothelioma therapy.