Peroxisome proliferator-activated receptor gamma as a therapeutic target for hepatocellular carcinoma: Experimental and clinical scenarios

Figure 1 General structure and ligand-activated transcription of peroxisome proliferator-activated receptor-gamma. A: Peroxisome proliferator-activated receptor (PPAR) structure includes four distinct structural domains A/B, C, D, and E/F; B: Ligand-activated transcription of PPARγ, which includes heterodimerization with nuclear receptor retinoid X receptor (RXR) and binding with peroxisome proliferator response elements located in the target genes through the DNA-binding domain (DBD). In the absence of ligand, PPAR is linked with the corepressor complex, whereas, in the presence of ligand, it is associated with the coactivator complex. LBD: Ligand-binding domain; PPRE: Peroxisome proliferator response element.

Figure 2 Schematic diagram showing the protective effect of peroxisome proliferator-activated receptor γ against the progression of hepatocellular carcinoma. Activated peroxisome proliferator-activated receptor γ (PPARγ) interacts with multiple pathways, leading to cell cycle arrest, apoptosis, inhibition of cell proliferation, and cell metastasis in hepatocellular carcinoma. BAX: B-cell lymphoma 2 (Bcl-2)-associated X protein; IκBα: Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibition alpha; IL: Interleukin; TIMP: Tissue inhibitor of metalloproteinases; MMP: Matrix metalloproteinase; ECM: Extracellular matrix; αSMA: Alpha-smooth muscle actin; TGFβ: Transforming growth factor beta; iNOS: Inducible nitric oxide synthase; TNFα: Tumor necrosis factor alpha; APF1: Apoptotic protease activating factor 1.