title: Effects of cisplatin and panobinostat on human mesothelial (Met-5A) and malignant pleural mesothelioma (MSTO-211H) cells.
abstract: New therapeutic approaches are still needed for effective malignant pleural mesothelioma treatment. The use of classical chemotherapy agents in combination with newly developed molecules may shed light on new therapeutic approaches. We aimed to determine the efficacy of panobinostat, alone and in combination with cisplatin, on cell survival and mRNA expression of FOXO3A, CCND1, and CASP9 genes in both mesothelioma and healthy mesothelial cell lines. Cells were treated with 1-100 µM cisplatin and 25-1000 nM panobinostat. Methylthiazol tetrazolium assays were performed to determine cell viability. mRNA expression levels of genes were analyzed with quantitative real-time polymerase chain reaction. Cisplatin and panobinostat exposure of the cells for 24 h resulted in decreased cell survival. The combined treatment was found to be more effective. No significant changes were observed with respect to CCND1 expression after exposure to agents alone or in combination. However, agents in combination resulted in upregulation of FOXO3A and CASP9 in MSTO-211H cells. Gene expression levels were not affected by any agents in healthy cells. Use of cisplatin in combination with new chemotherapeutic agents may reduce the toxic effects of cisplatin in normal cells and result in more effective removal of tumor cells.
authors.affiliation: Phase IV Students, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey.
authors.forename: K E
authors.initials: KE
authors.lastname: Gultekin
authors.forename: M K
authors.initials: MK
authors.lastname: Yurdakonar
authors.forename: E
authors.initials: E
authors.lastname: Yaman
authors.forename: U S
authors.initials: US
authors.lastname: Yuce
authors.forename: A
authors.initials: A
authors.lastname: Yilmaz
authors.forename: E
authors.initials: E
authors.lastname: Alp
authors.forename: A
authors.initials: A
authors.lastname: Celik
authors.forename: S M
authors.initials: SM
authors.lastname: Demiroz
authors.forename: H I
authors.initials: HI
authors.lastname: Onen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008654:Mesothelioma / Q000188:drug therapy / Q000378:metabolism; D000077767:Panobinostat; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D006877:Hydroxamic Acids; D007211:Indoles; D012333:RNA, Messenger; D019938:Cyclin D1; D000077767:Panobinostat; C506433:CASP9 protein, human; D053453:Caspase 9; D002945:Cisplatin