ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors around the world. The emergence of immune checkpoint inhibitors targeting programmed death-1/programmed death-ligand 1 and cytotoxic T lymphocyte-associated antigen-4 has brought great breakthroughs in the treatment of HCC. However, since HCC is a type of tumor with high heterogeneity, monotherapy is only effective for a small number of patients and may not be able to achieve long-lasting benefits due to drug resistance, and therefore, it is necessary to explore the potential of new immune checkpoint inhibitors in the prevention and treatment of HCC. This article analyzes and summarizes the biological characteristics of the new immune checkpoints T cell immunoglobulin and ITIM domain (TIGIT), V-domain immunoglobulin suppressor of T-cell activation (VISTA), B and T lymphocyte attenuator (BTLA), and B7 homologous protein-4 (B7-H4) and their expression and function in HCC. The analysis shows that TIGIT, VISTA, BTLA, and B7-H4 are highly expressed in HCC tissue and are associated with the prognosis of HCC patients, and targeted blocking of corresponding pathways can effectively inhibit the progression of HCC, suggesting that these molecules are potential targets for tumor treatment and that in-depth studies can provide new directions for HCC immunotherapy.
ABSTRACT
Objective To adopt the expression profile chip to investigate the effect of Rabdosia serra (Maxim.) hara water extract on related gene of human hepatocellular carcinoma(HCC) HepG2 cells for researching the possible mechanism of its water extract on HCC.Methods The human HCC HepG2 cells were cultured in vitro.After adding Rabdosia serra (Maxim.) hara water extract (9.54 mg/mL) for 24 h action,the expression profile chip was adopted to detect the HepG2 gene change after Rabdosia serra (Maxim.) hara action and then the chip results were verified by using RT-PCR and Western blot.Results The phase contrast microscope observation found that compared with the negative control group,the number of HepG2 cells was significantly reduced after Rabdosia serra (Maxim.) hara water extract action.The expression profile results showed that after Rabdosia serra (Maxim.)hara water extract action for 24 h,264 genes were risen to over twice folds compared with the negative control group and 194 genes were decreased by over twice folds compared with the negative control group.The gene ontology(GO) and KEGG analysis indicated that Rabdosia serra (Maxim.) hara could up-regulate multiple genes in DUSPs and IGFBPs family and down-regulate multiple genes in MCMs family.The RT-PCR detection found that compared with the negative control group,DUSP1 and IGFBP1 in the Rabdosia serra (Maxim.) hara treatment group were increased,while FXR and ALDH8A1 were decreased (P＜0.01),which were consistent with the results of expression profile chip.The Western blot results found that the protein expression level of DUSP1 in the Rabdosia serra (Maxim.) hara treatment group was also significantly higher than that in the negative control group (P＜ 0.01).Conclusion The expression profile chip shows that Rabdosia serra (Maxim.) hara can inhibit the proliferation of HCC cells by regulating multiple genes.
ABSTRACT
AIM: To activate hepatic stellate cells (HSC) in vitro in precision-cut liver slices (PCLS) stimulated by acetaldehyde for studying and screening anti-fibrotic drugs. METHODS: PCLS were prepared by the vibratome, and incubated with 700 ?m?L~-1 acetaldehyde for 0, 2, 4 and 6 h. The medium and homogenate were retained to determine glutathione S-transferase (GST) activity, lactate dehydrogenase (LDH) leakage and hydroxyproline (Hyp) content. PCLS were prepared for paraffin sections. The expression of ?-smooth muscle actin (?-SMA) was evaluated by immunohistochemistry, and the result was analyzed with image analysis software. RESULTS: The leakages of GST and LDH were increased significantly compared with those in 0 h group (P
ABSTRACT
Aim The changes and characteristics of liver drug-metabolizing and antioxiditive functions in different status of hepatic injury was investigated to provide support for clinical drug treatments in hepatic fibrosis. Methods Carbon tetrachloride (CCl 4) and other mixture factors were used to make animal model of acute hepatic injury, hepatic fibrosis and cirrhosis, respectively. Subcelluar fractions of liver were prepared by differential centrifugation. Activities of drug-metabolizing and antioxidative enzymes were monitored. Results Levels of phase I enzymes-cytochrome P450 (CYP), CYP1A1 (7-ethoxyresorufin O-deethylation), CYP2E1 (aniline hydroxylation), CYP3A1/2 (erythromycin N-demethylation), and phase Ⅱ enzymes-glutathione S-transferase (GST) were reduced remarkably in hepatic microsomes in different hepatic injury status in a time-dependent manner. However, the activity of CYP2E1 came to be the lowest in acute hepatic injury and recovered gradually when injury time was prolonged. In hepatic fibrosis, the activities of CYP1A,CYP2E1,CYP3A and GST reached 68%,56%,81% and 59%, respectively, of the control, and the functions of antioxidative enzymes in cytosol GST,catalase(Cat) and glutathione peroxidase(GSH-Px) declined to 85%,76% and 54%, respectively, of the control. Conclusion The xenobiotic-metabolizing abilities in liver with hepatic fibrosis were distinctly decreased, which constantly relates with the degrees and the lengths of hepatic injury.