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

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dc.authoridEmine Tural / 0000-0003-3624-1378
dc.authoridNazlı Çil / 0000-0002-2164-8688
dc.authoridMücahit Seçme / 0000-0002-2084-760X
dc.authoridGülçin Abban Mete / 0000-0001-6794-3685
dc.authoridHakan Darici / 0000-0001-9393-554X
dc.authoridAyhan Bilir / 0009-0009-9399-5927
dc.authoridErdal Karaoz / 0000-0002-9992-833X
dc.authorscopusidHakan Darici / 22333489600
dc.authorwosidHakan Darici / AAG-4316-2019
dc.contributor.authorTural, Emine
dc.contributor.authorÇil, Nazlı
dc.contributor.authorSeçme, Mücahit
dc.contributor.authorMete, Gülçin Abban
dc.contributor.authorDarici, Hakan
dc.contributor.authorBilir, Ayhan
dc.contributor.authorKaraoz, Erdal
dc.date.accessioned2025-04-18T09:03:36Z
dc.date.available2025-04-18T09:03:36Z
dc.date.issued5 Temmuz 2024
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, P53, 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.issue3
dc.identifier.scopus2-s2.0-85198984801
dc.identifier.startpage560
dc.identifier.trdizinid1249395
dc.identifier.urihttps://doi.org/10.31362/patd.1490977
dc.identifier.urihttps://dergipark.org.tr/tr/pub/patd/issue/83803/1490977
dc.identifier.urihttps://hdl.handle.net/20.500.12713/6678
dc.identifier.volume17
dc.indekslendigikaynakScopus
dc.indekslendigikaynakTR-Dizin
dc.institutionauthorDarici, Hakan
dc.institutionauthorKaraoz, Erdal
dc.institutionauthoridHakan Darici / 0000-0001-9393-554X
dc.institutionauthoridErdal Karaoz / 0000-0002-9992-833X
dc.language.isoen
dc.publisherPamukkale Üniversitesi
dc.relation.ispartofPamukkale Tıp Dergisi
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectEndometrial cancer
dc.subjectPI3K/AKT/mTOR pathway
dc.subjecteverolimus
dc.subjectmetformin
dc.subjectlithium
dc.titleThe effects of lithium, metformin and everolimus substances on cell growth in 2D and 3D Ishikawa endometrial carcinoma cell culture
dc.title.alternativeLityum, metformin ve everolimus maddelerinin 2D ve 3D Ishikawa endometrial karsinom hücre kültüründe hücre büyümesi üzerine etkileri
dc.typeArticle

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