The investigation of the effects of Metformin in Thyroid Cancer
Abstract
Background: Thyroid cancer is generally associated with an excellent prognosis, but there is significant long-term morbidity with standard treatment, and some sub-types have poor prognosis.Metformin, an oral anti-diabetic drug is shown to have anti-cancer effects in several types of cancer (breast, lung and ovarian cancer).Proposed mechanisms include activation of Adenosine Mono-phosphate-activated Protein Kinase (AMPK) pathway; inhibition of mTOR pathway; reduction in blood glucose and insulin levels by inhibiting hepatic gluconeogenesis and increasing peripheral glucose uptake.OCT1 (organic cation transporter 1) helps in the uptake of Metformin into liver cells.Aims: Explore the anti-cancer effect of Metformin on the growth and proliferation of thyroid cancer cell lines.Methods: The effects of Metformin on thyroid cancer cell lines (FTC-133, K1E7, RO82-W-1, 8305C and TT) and normal thyroid follicular cells (Nthy-ori 3-1) were investigated using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay for cell proliferation; clonogenic assay; Fluorescence-activated Cell Sorting (FACS) analysis for apoptosis (using double staining with Annexin V-FITC stained early apoptotic cells and propidium iodide stained late apoptotic cells) and cell cycle (using propidium iodide staining); and H2A.X phosphorylation (γH2AX) assay for DNA repair.Immunocytochemistry was used to investigate OCT1 expression to evaluate the mechanism of action of Metformin.The effects of…
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