Doksorubisinin Luminal A ve Üçlü Negatif Meme Kanseri Hücrelerinde p53 Apoptoz Yolağı ve Çoklu İlaç Direnci Üzerinde Farklı Etkilerinin İncelenmesi

Abstract

Breast cancer is the most common diagnosed cancer type amongst women. Although it is known that cell signaling pathways such as apoptosis, necrosis, and regulation cell cycle are known to be influental on breast cancer development, the detailed mechanism is yet to be deciphered. In the present thesis, low doses of doxorubicin, a chemotherapeutic agent, were applied to MCF-7 and MDA-MB-231 breast cancer cell lines. Subsequent to observation of death of both cell lines, viability and apoptosis designation assays were handled in order to determine the dominant death mechanism. After both cell lines were treated with low doses of doxorubicin, live cell percentages were dropped especially in MCF-7 and this effect was primarly caused by necrosis. Bax/Bcl-2 ratio which is an apoptotic marker was increased by 2,74 and 1,74 fold in MCF-7 and MDA-MB-231 cells, respectively although cytochrome c release and caspase 8/9 levels were not altered indicating that these doses are not enough to effectively initiate apoptosis. As multidrug resistance is an important obstacle in cancer treatment, both drug efflux from cells and expression level of a multidrug resistance gene, Mdr-1, were investigated. It was clear that conspicuously high levels of drug resistance is an important factor for MDA-MB-231 cells to be affected less by the events of apoptosis and necrosis. In conclusion, the effect of applied sub-clinical doses of doxorubicin on triple negative MDA-MB-231 cells which possess mutant p53 and vivid resistance potential is significantly subdued.