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

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• The PI3K/AKT/FOXO signaling pathway is crucial for tumor cell survival, proliferation, and apoptosis.
• Metformin's potential to modulate insulin-driven cancer cell growth via this pathway requires investigation.

Purpose of the Study:

• To investigate the effect of metformin on insulin-promoting cell growth in anaplastic thyroid cancer.
• To determine if metformin regulates the PI3K/AKT/FOXO signaling pathway in this context.

Main Methods:

• Anaplastic thyroid cancer cells were treated with varying concentrations of metformin over different time periods.
• Cell viability, morphology, apoptosis, and migration were assessed using MTT assays, microscopy, AnnexinV-PI staining, and wound healing assays.
• Gene expression of PI3K, AKT, and FOXO1 was analyzed by RT-qPCR, and protein phosphorylation by ELISA.

Main Results:

• Metformin significantly decreased cell viability and migration in a time- and dose-dependent manner, inducing apoptosis and morphological changes.
• Metformin inhibited the expression of PI3K, AKT, and FOXO1 genes (P < 0.05), with no significant change in AKT expression in the C643 cell line (P > 0.05).
• No significant effects on the phosphorylated levels of PI3K, AKT, and FOXO1 were observed following metformin treatment (P > 0.05).

Conclusions:

• Metformin intensifies FOXO1 downregulation, but this did not correlate with increased cell viability.
• The precise molecular mechanism by which metformin inhibits the PI3K/AKT pathway and reduces cell viability is not fully elucidated.
• Further research is necessary to clarify the exact molecular mechanisms involved.