The effects of lithium, metformin and everolimus substances on cell growth in 2D and 3D Ishikawa endometrial carcinoma cell culture
Küçük Resim Yok
Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Pamukkale University
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Purpose: 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.
Açıklama
Anahtar Kelimeler
Endometrial Cancer, Everolimus, Lithium, Metformin, PI3K/AKT/mTOR Pathway
Kaynak
Pamukkale medical journal
WoS Q Değeri
Scopus Q Değeri
Q4
Cilt
17
Sayı
3
Künye
Tural, 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.
