Synergistic antitumor effects of quercetin and triptolide in hepatocellular carcinoma via modulation of PI3K/AKT/mTOR and Nrf2 signaling pathways

Figure 1 Schematic illustration of the interplay between the phosphatidylinositol 3-kinase/protein kinase B/ mammalian target of rapamycin and nuclear factor erythroid 2-related factor 2 signaling pathways. Phosphatidylinositol 3-kinase activation induces protein kinase B phosphorylation, leading to mammalian target of rapamycin signaling and regulation of cell proliferation, survival, and cell cycle progression, while phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase acts as a negative regulator. Mammalian target of rapamycin also influences hypoxia-inducible factor 1-alpha activity. Oxidative stress impairs nuclear factor erythroid 2-related factor 2 nuclear translocation, reducing antioxidant responses. Interactions involving glycogen synthase kinase 3 and nuclear factor kappa B further link these pathways to inflammation and cell fate regulation. PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; PTEN: Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase; HIF-1α: Hypoxia-inducible factor 1-alpha; GSK3: Glycogen synthase kinase 3; mTOR: Mammalian target of rapamycin; Nrf2: Nuclear factor erythroid 2-related factor 2; NF-κB: Nuclear factor kappa B; NOS: Nitric oxide synthase.