The effects of lithium, metformin and everolimus substances on cell growth in 2D and 3D Ishikawa endometrial carcinoma cell culture

dc.authorscopusidErdal Karaöz / 7003448087
dc.authorscopusidHakan Darıcı / 22333489600
dc.authorwosidErdal Karaöz / IXE-6677-2023
dc.authorwosidHakan Darıcı / AAG-4316-2019
dc.contributor.authorTural, Emine
dc.contributor.authorÇil, Nazlı
dc.contributor.authorSeçme, Mücahit
dc.contributor.authorAbban Mete, Gülçin
dc.contributor.authorDarıcı, Hakan
dc.contributor.authorBilir, Ayhan
dc.contributor.authorKaraöz, Erdal
dc.date.accessioned2025-04-18T09:44:09Z
dc.date.available2025-04-18T09:44:09Z
dc.date.issued2024
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü
dc.description.abstractPurpose: Our aim is to study the effects of the single and combined treatments of Everolimus, Metformin, and Lithium Chloride in two-dimensional (2D, monolayer) and three-dimensional (3D, spheroid) cell cultures of Ishikawa cells, which comprise the endometrial cancer cell line. Materials and methods: As part of the study, the effects of single and combined forms of Everolimus, Metformin, and Lithium Chloride were determined on cell viability, invasion, colony formation and apoptosis, and PI3K/AKT/ mTOR pathway. Cell viability was assessed using XTT assay. CASP3, CASP8, CASP9, FASL, FADD, TNF, TRADD, BAX, TP53, PI3KCA, PI3KCB, PTEN, MTOR, AKT1 genes were evaluated with RT-PCR, apoptosis was evaluated by flow cytometry and 3D spheroid results were evaluated with invert microscope analysis. Results: Everolimus, metformin, and lithium's IC50 levels were found at 48 hours to be 37.46 nM, 48.59 mM, and 100 µM, respectively. It was determined that the invasive capacities of Ishikawa cells in treatment groups, as well as cell colony formation were significantly reduced. In addition, Ishikawa spheroid cells were significantly suppressed compared with the control groups. RT-PCR results revealed that substances and their combinations affect genes associated with PI3K/AKT/mTOR pathway and apoptosis. Flow cytometry results showed notably increased apoptosis by single and combined treatments. Conclusion: As a result, the single and combination forms of everolimus, metformin, and lithium have reduced cell proliferation, induced apoptosis, and decreased mTOR activation through various mechanisms in Ishikawa cells. However, our study has shown that Eve alone and triple combination therapy (Eve+Met+Lit) are more effective than other therapies in the treatment of endometrial cancer.
dc.identifier.citationTural, E., Çil, N., Seçme, M., Mete, G. A., Darici, H., Bilir, A., & Karaoz, E. (2024). The effects of lithium, metformin and everolimus substances on cell growth in 2D and 3D Ishikawa endometrial carcinoma cell culture. Pamukkale Medical Journal, 17(3), 560-576.
dc.identifier.doi10.31362/patd.1490977
dc.identifier.endpage576
dc.identifier.issn13099833
dc.identifier.issue3
dc.identifier.scopus10.31362/patd.1490977
dc.identifier.scopusqualityQ4
dc.identifier.startpage560
dc.identifier.urihttp://dx.doi.org/10.31362/patd.1490977
dc.identifier.urihttps://hdl.handle.net/20.500.12713/6841
dc.identifier.volume17
dc.indekslendigikaynakScopus
dc.institutionauthorKaraöz, Erdal
dc.institutionauthorDarıcı, Hakan
dc.institutionauthoridErdal Karaöz / 0000-0002-9992-833X
dc.institutionauthoridHakan Darıcı / 0000-0001-9393-554X
dc.language.isoen
dc.publisherPamukkale University
dc.relation.ispartofPamukkale medical journal
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectEndometrial Cancer
dc.subjectEverolimus
dc.subjectLithium
dc.subjectMetformin
dc.subjectPI3K/AKT/mTOR Pathway
dc.titleThe effects of lithium, metformin and everolimus substances on cell growth in 2D and 3D Ishikawa endometrial carcinoma cell culture
dc.typeArticle

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