CD147 promotes cervical cancer migration and invasion by up-regulating fatty acid synthase expression.

CD147 is a transmembrane glycoprotein that when highly expressed contributes to tumor progression. In the present study, we investigate the clinical relevance of CD147 expression in CCSC tissues and evaluate the association between CD147 expression and cervical lymph node metastasis; CD147 was detected using immunohistochemistry. To functionally analyze the role of CD147 in CCSC cell lines in vitro, SiHa cells were employed, whose endogenous CD147 was artificially downregulated, by using lentiviral-based transfection. Moreover, we have confirmed that knockdown of CD147 led to reduced levels of cellular lipid content in shCD147 cells by BODIPY staining. Cell invasion and migration were analyzed using transwell assays and wound healing. Angiogenesis and lymphangiogenesis were assessed by an endothelial cell tube formation assay. Our data showed that highly expressed CD147 up-regulated the major lipogenic genes, FAS and ACC1 to promote de novo lipogenesis, and knockdown of CD147 significantly inhibited the migration and invasion of CSCC cells. The culture supernatants of CD147 knockdown cells significantly inhibited vascular and lymphatic endothelial cell tube formation. Our results suggest that CD147-mediated FAS and ACC1 overexpression are major regulators of cervical cancer growth and metastasis.

The functional role of RNF113A in cervical carcinogenesis.

RNF113A is thought to function as an E3 ligase, engaged in the regulation of the turnover and activity of many target proteins. However, the fuctional role of RNF113A in cervical cancer remains unclear. In this study, by performing an immunohistochemistry (IHC) assay, we found that the RNF113A protein was significantly up-regulated in cervical cancer cells, and a high RNF113A expression was associated with malignant phenotypes. To determine the role of RNF113A in cervical cancer aggressiveness, we performed a gain and loss of functional experiments in cervical cancer cells with cell transfection, wound healing, transwell migration, and flow cytometry analysis. The results showed that RNF113A promotes the proliferation and survival ability of cervical cancer cells, enhances migration and invasion, and inhibits the apoptosis of cervical cancer cells. By silencing RNF113A in CSCC cell lines, we observed an up-regulation of the P53 protein level, indicating that P53 may function as a target of the RNF113A E3 ligase, and RNF113A may inhibit tumor cell apoptosis by degrading the TP53 protein.

Inhibitive effects of 15-deoxy-Δ(12),(14)-prostaglandin J2 on hepatoma-cell proliferation through reactive oxygen species-mediated apoptosis.

OBJECTIVE: 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) induces reactive oxygen species (ROS)-mediated apoptosis in many malignant cells, which has not been studied in hepatoma cells. In this study, we investigated whether 15d-PGJ2 induced apoptosis in hepatocellular carcinoma (HCC) associated with ROS. MATERIALS AND METHODS: The LM3, SMMC-7721, and Huh-7 HCC cell lines were treated with 15d-PGJ2 (5-40 µM) for 24, 48, and 72 hours. Cholecystokinin 8 was used to detect the cytotoxicity of 15d-PGJ2. Flow cytometry, Hoechst staining, and Western blotting were used to analyze apoptosis. ROS were combined with the fluorescent probe dihydroethidium and then observed by fluorescence microscopy and flow cytometry. Activation of JNK and expression of Akt were detected by Western blotting. RESULTS: 15d-PGJ2 inhibited HCC cell proliferation and induced apoptosis in a dose- and time-dependent manner. Apoptosis was mainly induced via an intrinsic pathway and was ROS-dependent, and was alleviated by ROS scavengers. ROS induced JNK activation and Akt downregulation in HCC cells. CONCLUSION: 15d-PGJ2 induced ROS in HCC cell lines, and inhibition of cell growth and apoptosis were partly ROS-dependent.

Systematic review and meta-analysis: bezafibrate in patients with primary biliary cirrhosis.

BACKGROUND AND AIM: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cirrhosis (PBC), but not all cases respond well. Evidence has shown that combination therapy of UDCA with bezafibrate significantly improved liver function. A meta-analysis was performed to assess the efficacy and safety of UDCA and bezafibrate combination therapy in the treatment of PBC. RESULTS: Nine trials, with a total of 269 patients, were included in the analysis. The bias risk of these trials was high. Compared with UDCA alone, the combination with bezafibrate improved the Mayo risk score (mean difference [MD], 0.60; 95% confidence interval [CI], 0.25-0.95; P=0.0008) and liver biochemistry: alkaline phosphatase (MD, -238.21 IU/L; 95% CI, -280.83 to -195.60; P<0.00001); gamma-glutamyltransferase (MD, -38.23 IU/L; 95% CI, -50.16 to -25.85; P<0.00001); immunoglobulin M (MD, -128.63 IU/L; 95% CI, -151.55 to -105.71; P<0.00001); bilirubin (MD, -0.20 mg/dL; 95% CI, -0.33 to -0.07; P=0.002); triglycerides (MD, -26.84 mg/dL; 95% CI, -36.51 to -17.17; P<0.0001); total cholesterol (MD, -21.58 mg/dL; 95% CI, -30.81 to -12.34; P<0.0001), and serum alanine aminotransferase (MD, -10.24 IU/L; 95% CI, -12.65 to -78.5; P<0.00001). However, combination therapy showed no significant differences in the incidence of all-cause mortality or pruritus, and may have resulted in more adverse events (risk ratio [RR], 0.22; 95% CI, 0.07-0.67; P=0.008). CONCLUSION: Combination therapy improved liver biochemistry and the prognosis of PBC, but did not improve clinical symptoms or incidence of death. Attention should be paid to adverse events when using bezafibrate.

Astaxanthin Inhibits Proliferation and Induces Apoptosis of Human Hepatocellular Carcinoma Cells via Inhibition of Nf-Κb P65 and Wnt/Β-Catenin in Vitro.

Hepatocellular carcinoma (HCC) is a malignant tumor that can cause systemic invasion; however, the exact etiology and molecular mechanism are unknown. Astaxanthin (ASX), a powerful antioxidant, has efficient anti-oxidant, anti-inflammatory, and other activities, and has great research prospects in cancer therapy. We selected the human hepatoma cell lines, LM3 and SMMC-7721, to study the anti-tumor effect and related mechanisms of ASX. The cell lines were treated with different concentrations of ASX, and its solvent DMSO as a control, for different time periods and the results were determined using CCK8, qRT-PCR, WB, apoptotic staining, and flow cytometry. ASX induced significant apoptosis of HCC cells, and its effect may have been caused by NF-κB p65 and Wnt/ß-catenin down-regulation via negative activation of PI3K/Akt and ERK. Antitumor research on ASX has provided us with a potential therapy for patients with hepatomas.

By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice.

Cancer cells exhibit an altered metabolic phenotype known as the aerobic glycolysis. The expression of HK2 changes the metabolic phenotype of cells to support cancerous growth. In the present study, we investigated the inhibitory effect of resveratrol on HK2 expression and hepatocellular carcinoma (HCC) cell glycolysis. Aerobic glycolysis was observed in four HCC cell lines compared to the normal hepatic cells. Resveratrol sensitized aerobic glycolytic HCC cells to apoptosis, and this effect was attenuated by glycolytic inhibitors. The induction of mitochondrial apoptosis was associated with the decrease of HK2 expression by resveratrol in HCC cells. In addition, resveratrol enhanced sorafenib induced cell growth inhibition in aerobic glycolytic HCC cells. Combination treatment with both reagents inhibited the growth and promoted apoptosis of HCC-bearing mice. The reduction of HK2 by resveratrol provides a new dimension to clinical HCC therapies aimed at preventing disease progression.

Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis.

OBJECTIVE: Astaxanthin, a potent antioxidant, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. However, its effect on concanavalin A (ConA)-induced autoimmune hepatitis remains unclear. The aim of this study was to investigate the protective effects of astaxanthin on ConA-induced hepatitis in mice, and to elucidate the mechanisms of regulation. MATERIALS AND METHODS: Autoimmune hepatitis was induced in in Balb/C mice using ConA (25 mg/kg), and astaxanthin was orally administered daily at two doses (20 mg/kg and 40 mg/kg) for 14 days before ConA injection. Levels of serum liver enzymes and the histopathology of inflammatory cytokines and other maker proteins were determined at three time points (2, 8 and 24 h). Primary hepatocytes were pretreated with astaxanthin (80 µM) in vitro 24 h before stimulation with TNF-α (10 ng/ml). The apoptosis rate and related protein expression were determined 24 h after the administration of TNF-α. RESULTS: Astaxanthin attenuated serum liver enzymes and pathological damage by reducing the release of inflammatory factors. It performed anti-apoptotic effects via the descending phosphorylation of Bcl-2 through the down-regulation of the JNK/p-JNK pathway. CONCLUSION: This research firstly expounded that astaxanthin reduced immune liver injury in ConA-induced autoimmune hepatitis. The mode of action appears to be downregulation of JNK/p-JNK-mediated apoptosis and autophagy.

Combination therapy of ursodeoxycholic acid and budesonide for PBC-AIH overlap syndrome: a meta-analysis.

In this study, a meta-analysis of randomized controlled trials comparing ursodeoxycholic acid (UDCA) monotherapy with combination therapies utilizing UDCA and budesonide was performed. We found that combination therapy with UDCA and budesonide was more effective than UDCA monotherapy for primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Moreover, compared to prednisone, budesonide has fewer side effects.