Effects of metformin on the PI3K/AKT/FOXO1 pathway in anaplastic thyroid Cancer cell lines
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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.
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). However, there was no significant change in the expression level of AKT following metformin treatment for C643 cell line (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).
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.
KeywordsAnaplastic thyroid Cancer Metformin PI3K AKT FOXO1
The authors are grateful to Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences Tehran, Iran for their excellent technical and financial supports. This manuscript was extracted from PhD thesis of Zahra Nozhat (grant No: 852). The authors wish to acknowledge Ms. Niloofar Shiva for editing of English grammar and syntax of the manuscript.
Compliance with ethical standards
Conflict of interest
There is no conflict of interest.
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