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.
Author: | Claudia BaronGND, Marie BuchholzORCiDGND, Britta Majchrzak-StillerORCiDGND, Ilka PetersORCiDGND, Daniel FeinGND, Thomas MüllerGND, Waldemar UhlORCiDGND, Philipp HöhnORCiDGND, Johanna Josefine StrotmannORCiDGND, Chris BraumannORCiDGND |
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URN: | urn:nbn:de:hbz:294-102418 |
DOI: | https://doi.org/10.3390/ijms23137293 |
Parent Title (English): | International journal of molecular sciences |
Subtitle (English): | a 3-D in vitro study |
Publisher: | MDPI |
Place of publication: | Basel, Schweiz |
Document Type: | Article |
Language: | English |
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 |
Volume: | 23 |
Issue: | 13, Article 7293 |
First Page: | 7293-1 |
Last Page: | 7293-16 |
Note: | 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): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |