Meme kanseri ve meme kanseri kök hücrelerinde telomeraz inhibitörü BIBR1532nin Wnt sinyal yolağı üzerindeki etkisi
Project no. 23721 · Status: Kapanmış · 2022
Summary
<p>Breast cancer is a leading disease in cancer-related deaths in women. It is one of the most common types of cancer in Turkey as it is in the whole world. Breast cancer and breast cancer stem cells are associated with tumor growth, multidrug resistance, metastasis, and relapse of cells, and targeting these cells in the treatment process is thought to be effective. Cancer stem cells are a subpopulation of cells within a tumor that create resistance to metastasis and therapy and are the cells responsible for tumor initiation. These cells, like stem cells, have self-renewal, proliferation, and differentiation properties. The Wnt Signaling Pathway is tightly linked to cancer and is associated with reduced survival in breast cancer patients, and this signaling pathway controls the properties of cancer stem cells. However, BIBR1532 is a telomerase inhibitor and is widely used in cancer research to inhibit active telomerase in tumors. It is a preferred telomerase inhibitor because it has few side effects in normal tissues. In our study, it is aimed to investigate the effect of telomerase inhibitor BIBR1532 on Wnt signaling pathway in breast cancer and breast cancer stem cells. First, the cytotoxicity of the active substance BIBR1532, which was applied to MCF-7, MCF10A (normal breast epithelial cells) and BCSCs (breast cancer stem cells), which we used in this study, was determined. The IC₅₀ doses of the cells whose apoptotic effects were investigated later, were found to be 34.59 μM in MCF-7 cells, 29.07 μM in MCF10A cells and 29.91 μM in BCSC line at 48th hour. Considering the apoptosis results, it was observed that apoptosis was severely induced in MCF-7 and BCSC lines, but not much change was observed in the MCF10A cell line. Gene expression changes in genes in the Wnt signaling pathway were determined by RT-qPCR. When the gene expression changes of the genes in the Wnt pathway in our study were examined, it was seen that some of the genes that we know to be oncogenes were downregulated, and some tumor-suppressing genes were up-regulated. Gene expression results obtained from genes that have not been studied much in breast cancer studies will also contribute to the literature in this sense.</p>