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- W3108359670 abstract "Background: In the last decades, metformin (Met), an herbal anti- diabetic medicine, has been proposed as an anti-cancer agent.Objective: Thyroid cancers are the most common malignancy of the endocrine system. Therefore, the current study was performed to assess the effects of Met on cell proliferation and activation of thePhosphoinositide 3-Kinase (PI3K)/Protein kinase B (AKT)/Forkhead Box O1 (FOXO1) signaling pathway in the Medullary Thyroid Carcinoma (MTC) cells. The effects of Met on the expression ofREarranged during Transfection (RET) proto-oncogene were also investigated.Methods: MTC cell line (TT) was treated with 0, 2.5, 5, 10, 20, 30, 40, 50, and 60 mM concentrations of Met for 24, 48, and 72 h. The viability and apoptosis of the treated cells were measured by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Annexin V-Propidium Iodide (PI) assays. The expression level of PI3K, AKT, FOXO1, and RET genes was investigated by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), and phosphorylation of their proteins was determined by the Enzyme-Linked Immunosorbent Assay (ELISA). Results: Results showed that Met significantly decreased the viability of the MTC cells. Met also reduced the expression level of PI3K, AKT, and FOXO1 genes (P<0.05), whereas it elevated the expression level of RET proto-oncogene (P<0.05). Conclusion: It seems that the Met has cytostatic effect on the TT cells. Our results showed that anti-tumoral effects of Met may be cell type-specific, and according to the induction of RET (as aproto-oncogene) and inhibition of FOXO1 (as a tumor suppressor gene), Met could not be an appropriate agent in treatment of MTC. The antineoplastic activity of Met has been confirmed againstseveral malignancies in “in vitro” and “in vivo” studies. However, its molecular mechanisms in the treatment of different carcinomas particularly in thyroid cancers are not clearly understood and morestudies are required to confirm its exact effect on the MTC." @default.
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- W3108359670 date "2020-11-27" @default.
- W3108359670 modified "2023-09-23" @default.
- W3108359670 title "Antineoplastic Activity of an Old Natural Antidiabetic Biguanoid on the Human Thyroid Carcinoma Cell Line" @default.
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