02. Master's Thesis

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Browsing 02. Master's Thesis by Subject "autophagy"

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    ELUCIDATION OF AUTOPHAGIC FLUX UNDER GLUCOSE AVAILABILITY
    (Nazarbayev University School of Medicine, 2024-04-26) Zhuban, Aigerim
    Autophagy, crucial for maintaining cell homeostasis and cell renovation, has a significant role in the pathophysiology of various diseases. However, the association between autophagy and glucose accessibility remains insufficiently researched. The main objective of the research is to investigate autophagic flux under different concentrations of glucose, with a particular focus on its implications for cancer and diabetes. The findings of this study were based on the analysis of autophagic flux dynamics performed in MDA-MB231 and MCF7 human breast cancer cell lines subjected to different concentrations of glucose in the culture media. The methodology consisted of advanced laboratory techniques like MTT Assay, Western blotting, and Immunofluorescence Staining. We hypothesized that the pathways of autophagy may alter based on the different glucose availability within a cell. Investigating these dynamics provided insights into the thorough understanding of glucose-mediated autophagy and its relationship with pathologies, especially diabetes and cancer. A comprehensive understanding of the role of glucose in autophagy may have more considerable implications in the fields of medicine and healthcare, particularly in the development of therapeutic approaches to conditions characterized by dysregulated glucose metabolism, such as diabetes. The shift from normal to high glucose conditions did not produce a significant or consistent change in the autophagic flux of the breast cancer cell lines. Consequently, the modifications in glucose concentration within the normal to high range are not sufficient to solely inhibit or induce autophagy in MCF-7 and MDA-MB231 breast cancer cells.
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    INVESTIGATING AUTOPHAGY AS A POTENTIAL PATHWAY OF ANTICANCER MECHANISM OF PHENFORMIN
    (Nazarbayev University School of Medicine, 2024) Khikhmetova, Kamila
    Phenformin, a representative of the biguanides class, is an anti-diabetic drug that was withdrawn from the market due to its side effects profile is currently being investigated as a potential anticancer agent. Autophagy is an evolutionary conserved mechanism of lysosome-mediated catabolic breakdown of proteins, cellular compartments, and infectious agents for maintaining homeostasis. Activation of autophagy in cancer cell could potentially be one of the mechanisms of phenformin’s anticancer activity. This research aimed to establish the antiproliferative activity of phenformin among different cancer cell lines and to study the effect of phenformin on expression of proteins involved in autophagy in cervical cancer cells. Cervical cancer is the fourth leading cause of cancer mortality as well as the fourth most diagnosed cancer type in females. Our findings demonstrate that phenformin decreases the proliferation of various cancer cell lines in a dose-dependent manner cells and may have an ability to increase autophagic flux in cervical cancer cells.