INVESTIGATION OF CYTOTOXIC AND APOPTOTIC EFFECTS OF AZD3463, A NEW ALK / IGF-1R INHIBITOR, IN NORMAL AND CANCER CELL LINES
Project no. 280 · Status: Kapanmış · 2017
Summary
Understanding the pathways involved in the development of breast cancer and the mechanisms of resistance development to chemotherapy have led to the search for new compounds targeting these pathways / mechanisms. AZD3463 is a compound inhibits ALK / IGF-1R. Since abnormal ALK activation and IGF-1 / IGF-1R are important pathways involved in the development of breast cancer, the study investigated the cytotoxic and apoptotic activity of AZD-3463, a compound acting on these two pathways, in MCF-7 and MCF-10a cells, and molecular mechanism was evaluated at the level of gene expression. For this purpose, the cytotoxic effect of AZD-3463 was evaluated spectrophotometrically by WST-1 test and apoptotic activity and mitochondrial membrane potential changes were evaluated by flow cytometry with Annexin-PI, JC-1 tests, respectively. Their effects on gene expression was investigated using qRT-PCR. In conclusion, we suggest that AZD3463 is an agent that can be used both alone and in combination with chemotherapotics currently used in the treatment of breast cancer with ALK / IGF1R inhibition. Further studies are needed on this subject.