Investigation of the Anticancer Effects of the Combination of PI3K Inhibitor and Ponatinib on the Chronic Myleoid Leukemia Cell Lines
Project no. 31880 · Status: Kapanmış (Yayın bekleniyor) · 2023
Summary
<p>This study aims to develop novel therapeutic strategies for the treatment of chronic myeloid leukemia (CML) by investigating the effects of ponatinib, an inhibitor of the BCR-ABL fusion gene, and LY294002, a synthetic molecule inhibitor targeting phosphoinositide 3-kinases (PI3Ks). Ponatinib is a targeted therapy used in cases where other tyrosine kinase inhibitors are ineffective or where drug resistance has developed due to mutations in the BCR-ABL gene. LY294002 targets PI3Ks, which play a significant role in cell growth, survival, and proliferation in various cancer types, including CML.</p><p>Initially, the optimal cell number per well for the experiments was determined through a proliferation assay. Subsequently, the cytotoxic effects of each compound were evaluated using the CCK-8 assay. Based on the obtained IC50 values, combination therapy was applied. The IC50 value for ponatinib in the K562 cell line was found to be 108.6 nM (at 48 hours), while the IC50 value for LY294002 was 45.88 μM (at 48 hours). The combination treatment of ponatinib and LY294002 demonstrated a more significant induction of apoptosis and inhibition of cell proliferation compared to the control group and individual treatments. The CFSE proliferation assay confirmed that this combination exerted a synergistic effect, leading to the greatest reduction in cell proliferation.</p><p>This study suggests that the combination of ponatinib and LY294002 may effectively inhibit the growth and survival of CML cells, contributing to the development of novel therapeutic strategies for the treatment of CML.</p>