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Substance GP-2250 as a New Therapeutic Agent for Malignant Peritoneal Mesothelioma—A 3-D In Vitro Study
- 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.
- Subjects :
- Mesothelioma
malignant peritoneal mesothelioma
spheroid model
in vitro
GP-2250
treatment
Mitomycin
Mesothelioma, Malignant
Organic Chemistry
Medizin
Antineoplastic Agents
General Medicine
Catalysis
Computer Science Applications
Inorganic Chemistry
Necrosis
Cell Line, Tumor
Antineoplastic Combined Chemotherapy Protocols
Humans
Cisplatin
Physical and Theoretical Chemistry
Molecular Biology
Peritoneal Neoplasms
Spectroscopy
Subjects
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