Zinc Oxide Nanoparticle Synergizes Sorafenib Anticancer Efficacy with Minimizing Its Cytotoxicity

Figure 4

Schematic diagram of the probable mechanism of synergy between ZnO-NPs and sorafenib. Sorafenib has antagonist effect on vascular endothelial growth factor receptor (VEGFR-β), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), epidermal growth factor receptor (EGFR), protooncogene B-Raf, and protein kinase B-1 (AKT-1). However, ZnO-NPs are involved in reactive oxygen species (ROS) generation and increased cell wall lipid peroxidation (LPO) leading to cytotoxic and genotoxic effects. MEK: mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; PI3K: phosphatidylinositol-3-kinase; PDK1: pyruvate dehydrogenase lipoamide kinase isozyme 1; mTOR: mammalian target of rapamycin; p53: tumor protein p53; BAD: BCL-2-associated death promoter.