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Substance GP-2250 as a New Therapeutic Agent for Malignant Peritoneal Mesothelioma—A 3-D In Vitro Study

Authors :
Claudia Baron
Marie Buchholz
Britta Majchrzak-Stiller
Ilka Peters
Daniel Fein
Thomas Müller
Waldemar Uhl
Philipp Höhn
Johanna Strotmann
Chris Braumann
Source :
International Journal of Molecular Sciences; Volume 23; Issue 13; Pages: 7293
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Malignant peritoneal mesothelioma is a rare tumor entity. Although cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have increased overall survival, its prognosis remains poor. Established chemotherapeutics include mitomycin C (MMC) and cisplatin (CP), both characterized by severe side effects. GP-2250 is a novel antineoplastic agent, currently under clinical investigation. This in vitro study aims to investigate effects of GP-2250 including combinations with CP and MMC on malignant mesothelioma. JL-1 and MSTO-211H mesothelioma cell lines were treated with increasing doses of GP-2250, CP, MMC and combination therapies of GP-2250 + CP/MMC. Microscopic effects were documented, and a flow-cytometric apoptosis/necrosis assay was performed. Synergistic and antagonistic effects were analyzed by computing the combination index by Chou-Talalay. GP-2250 showed an antiadhesive effect on JL-1 and MSTO-211H spheroids. It had a dose-dependent cytotoxic effect on both monolayer and spheroid cultured cells, inducing apoptosis and necrosis. Combination treatments of GP-2250 with MMC and CP led to significant reductions of the effective doses of CP/MMC. Synergistic and additive effects were observed. GP-2250 showed promising antineoplastic effects on malignant mesothelioma cells in vitro especially in combination with CP/MMC. This forms the basis for further in vivo and clinical investigations in order to broaden treatment options.

Details

ISSN :
14220067
Volume :
23
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences
Accession number :
edsair.doi.dedup.....95c36b065033ce51c978f74c9be0391c
Full Text :
https://doi.org/10.3390/ijms23137293