Enhancing Apoptosis and Ferroptosis: Synergistic Effects of Sorafenib and Dasatinib Nano-systems in Overcoming Drug Resistance in MULV-4 Cell lines

Sorafenib, a tyrosine kinase inhibitor used in hepatic and hematologic malignancies, often leads to drug resistance in cancer cells over time. This study explores the synergistic effects of sorafenib, dasatinib, and their respective PCL-based nano-systems in overcoming resistance mechanisms. The research reveals an orchestrated modulation of gene expression, upregulating pro-apoptotic genes like Bax and downregulating anti-apoptotic genes such as GPX4, NRF2, and SLC7A11, resulting in cancer cell death. These treatments enhance apoptosis, elevate ROS levels, reduce GPX4 activity, and inhibit colony formation, suggesting a dual induction of ferroptosis and apoptosis pathways. The study underscores the potential of nanocarriers in enhancing the efficacy of sorafenib and dasatinib against resistant cancer cells, providing insights into the molecular mechanisms underlying their anti-cancer effects.