BEZ235 Increases the Sensitivity of Hepatocellular Carcinoma to Sorafenib by Inhibiting PI3K/AKT/mTOR and Inducing Autophagy

Figure 8

Schematic diagram of the PI3K/AKT/mTOR and autophagy signal pathway. The combination of growth factors and receptors activates the cascade of the PI3K signaling pathway and promotes cell survival, proliferation, and migration. In cell-cycle regulation, GSK3β reduces the expression of cyclin D1, thereby inhibiting Rb phosphorylation and blocking the cell cycle. In HCC cells that have chemotherapy resistance to sorafenib, the use of sorafenib can abnormally activate PI3K/AKT/mTOR and induce insignificant autophagy. Sorafenib combined with BEZ235 targets a variety of molecules, inhibits PI3K, and enhances autophagy to inhibit cell proliferation, migration, and cell-cycle progression. Activation of caspase-9 and caspase-7 leads to cell apoptosis.