Year: 2018
Type: dissertation
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 Thyroid Stimulating Hormone (TSH), insulin and Insulin-like Growth Factor-1 (IGF-1) on the response to Metformin treatment were also investigated.Affymetrix assay was used for gene expression profiling of cell lines before and after Metformin treatment.Results: Metformin inhibited cell proliferation and colony formation at a minimum concentration of 0.03 mM and increased the percentage of apoptotic
Author: Safar Kheder
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2909950950