Alessia Bertoldo

University of Turin

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Riccarda Granata

University of Turin

Ezio Ghigo

University of Turin

Iacopo Gesmundo

University of Turin

Francesca Pedrolli

University of Turin

Giuseppina Granato

University of Turin

Silvia Deaglio

University of Turin

Renzhi Cai

University of Miami

Andrew V. Schally

University of Miami

Giulia Orlando

University of Turin

Wei Sha

University of Miami

Cooperative Institutions

University of Turin

Azienda Ospedaliera Citta' della Salute e della Scienza di Torino

Azienda Ospedaliero Universitaria San Giovanni Battista

South Florida Veterans Affairs Foundation for Research and Education

Diabetes Australia

Istituti di Ricovero e Cura a Carattere Scientifico

Ospedale San Luigi Gonzaga

Candiolo Cancer Institute

University of Miami

Miami VA Healthcare System

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Antagonist of Growth Hormone-Releasing Hormone Potentiates the Antitumor Effect of Pemetrexed and Cisplatin in Pleural Mesothelioma

International Journal of Molecular Sciences (2022)

Iacopo Gesmundo Francesca Pedrolli Nicoletta Vitale Alessia Bertoldo Giulia Orlando

Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis and no effective therapies, mainly caused by exposure to asbestos. Antagonists of growth hormone-releasing hormone (GHRH) display strong antitumor effects in many experimental cancers, including lung cancer and mesothelioma. Here, we aimed to determine whether GHRH antagonist MIA-690 potentiates the antitumor effect of cisplatin and pemetrexed in PM. In vitro, MIA-690, in combination with cisplatin and pemetrexed, synergistically reduced cell viability, restrained cell proliferation and enhanced apoptosis, compared with drugs alone. In vivo, the same combination resulted in a strong growth inhibition of MSTO-211H xenografts, decreased tumor cell proliferation and increased apoptosis. Mechanistically, MIA-690, particularly with chemotherapeutic drugs, inhibited proliferative and oncogenic pathways, such as MAPK ERK1/2 and cMyc, and downregulated cyclin D1 and B1 mRNAs. Inflammatory pathways such as NF-kB and STAT3 were also reduced, as well as oxidative, angiogenic and tumorigenic markers (iNOS, COX-2, MMP2, MMP9 and HMGB1) and growth factors (VEGF and IGF-1). Overall, these findings strongly suggest that GHRH antagonists of MIA class, such as MIA-690, could increase the efficacy of standard therapy in PM.

Pemetrexed

10.3390/ijms231911248

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Citations (10)

Growth hormone-releasing hormone (GHRH) promotes transdifferentiation of myoblasts and white adipocytes into brown/beige adipocytes

Endocrine Abstracts (2024)

Alessia Bertoldo Giuseppina Granato Iacopo Gesmundo Ezio Ghigo Riccarda Granata

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Transdifferentiation

White (mutation)

Growth hormone–releasing hormone

10.1530/endoabs.99.oc13.6