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Effects of metformin on the PI3K/AKT/FOXO1 pathway in anaplastic thyroid Cancer cell lines.


ABSTRACT:

Background

The PI3K/AKT/FOXO signaling pathway plays an important role in the survival, proliferation and apoptosis of tumor cells. The aim of the present study was to explore whether metformin could affect insulin-promoting cell growth by regulation of this pathway.

Material and methods

Anaplastic thyroid cancer cells were treated with 0-60 mM metformin for 24, 48 and 72 h. Cell viability, morphology, apoptosis and migration were investigated by MTT assay, microscopy observation, AnexinV-PI and the wound healing assay, respectively. Expression levels of PI3K, AKT and FOXO1 were detected by RT-qPCR, and proteins phosphorylated levels were determined by ELISA.

Results

Metformin decreased cell viability and migration in a significant time-and dose-dependent manner, and induced apoptosis and morphological changes in the cells. RT-qPCR results showed that expression levels of PI3K, AKT and FOXO1 was inhibited by metformin (P??0.05). ELISA results showed that metformin treatment had no significant effects on the phosphorylated levels of PI3K, AKT and FOXO1 (P?>?0.05).

Conclusuion

The downregulation of FOXO1 was intensified by metformin, but no increase in cell viability was observed following FOXO1 downregulation by metformin. However, the exact molecular mechanism of metformin on inhibition of the PI3K/AKT pathway and subsequent decrease in cell viability remains unclear and further studies are required for its clarification.

SUBMITTER: Nozhat Z 

PROVIDER: S-EPMC6279666 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Effects of metformin on the PI3K/AKT/FOXO1 pathway in anaplastic thyroid Cancer cell lines.

Nozhat Zahra Z   Mohammadi-Yeganeh Samira S   Azizi Feridoun F   Zarkesh Maryam M   Hedayati Mehdi M  

Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 20180921 2


<h4>Background</h4>The PI3K/AKT/FOXO signaling pathway plays an important role in the survival, proliferation and apoptosis of tumor cells. The aim of the present study was to explore whether metformin could affect insulin-promoting cell growth by regulation of this pathway.<h4>Material and methods</h4>Anaplastic thyroid cancer cells were treated with 0-60 mM metformin for 24, 48 and 72 h. Cell viability, morphology, apoptosis and migration were investigated by MTT assay, microscopy observation,  ...[more]

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