Substance GP-2250 as a new therapeutic agent for malignant peritoneal mesothelioma

  • 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.

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Author:Claudia BaronGND, Marie BuchholzORCiDGND, Britta Majchrzak-StillerORCiDGND, Ilka PetersORCiDGND, Daniel FeinGND, Thomas MüllerGND, Waldemar UhlORCiDGND, Philipp HöhnORCiDGND, Johanna Josefine StrotmannORCiDGND, Chris BraumannORCiDGND
Parent Title (English):International journal of molecular sciences
Subtitle (English):a 3-D in vitro study
Place of publication:Basel, Schweiz
Document Type:Article
Date of Publication (online):2023/10/17
Date of first Publication:2022/06/30
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
GP-2250; in vitro; malignant peritoneal mesothelioma; spheroid model; treatment
Issue:13, Article 7293
First Page:7293-1
Last Page:7293-16
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:St. Josef-Hospital Bochum, Klinik für Allgemein- und Viszeralchirurgie
Dewey Decimal Classification:Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International