Total flavonoids of Radix Tetrastigma suppress inflammation-related hepatocellular carcinoma cell metastasis.

This study aimed to investigate the effects of the total flavonoids of Radix Tetrastigma (RTF) on inflammation-related hepatocellular carcinoma (HCC) development. Extracted RTF was diluted to different concentrations for subsequent experiments. HCC cells were cotreated with lipopolysaccharide (LPS) and RTF to investigate the effects of RTF on LPS-stimulated HCC cells. A CCK-8 kit was used to measure cell proliferation. Apoptosis was detected with a flow cytometer. Cell migration and invasion were quantified by wound healing and Transwell assays, respectively. The expression of TLR4 and COX-2 and activation of the NF-κB pathway were determined by Western blotting. Treatment with LPS significantly enhanced cell proliferation and decreased the apoptosis rate, while cell migration and invasion were notably upregulated. RTF suppressed the proliferation and invasion induced by LPS stimulation and promoted HCC cell apoptosis. The protein levels of Bax and cleaved caspase-3 were decreased and that of Bcl-2 was increased by LPS in HCC cells, which could be rescued by RTF. RTF significantly inhibited the LPS-induced expression of the proinflammatory mediators IL-6 and IL-8 in HCC cells. Mechanistically, with RTF treatment, the upregulated expression of TLR4 and COX-2 induced by LPS was obviously downregulated. Furthermore, the phosphorylation of NF-κB/p65 was significantly decreased in LPS-stimulated cells after supplementation with RTF. Our study suggests that RTF exerts a significant inhibitory effect on the LPS-induced enhancement of the malignant behaviors of HCC cells via inactivation of TLR4/NF-κB signaling. RTF may be a promising chemotherapeutic agent to limit HCC development and inflammation-mediated metastasis.

Effects of the OPRM1 A118G Polymorphism (rs1799971) on Opioid Analgesia in Cancer Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: Although previous studies have demonstrated that the OPRM1 A118G polymorphism may influence the analgesia response to cancer pain, the results are inconsistent. In this article we aimed to fully examine the association between OPRM1 A118G (rs1799971) polymorphism and opioid analgesia by analyzing published information. This will provide information for better cancer pain management. MATERIALS AND METHODS: A systematic search of the literature dating to August 31, 2017 was conducted using PubMed, EMBase, Sinomed, and the Cochrane Library databases. The standardized mean difference (SMD) of required amounts of opioids between AA homozygotes and the G-allele was calculated. Subgroup analyses for race and opioid use was performed. In addition, drug sensitivity analysis, heterogeneity description, and publication bias assessment were performed. RESULTS: Of the 467 screened studies, 12 including 2118 participants were eligible to be included in our analysis. The meta-analysis results indicated that G-allele carriers (AG+GG) of the OPRM1 A118G polymorphism required higher opioid doses for pain management than those with the AA homozygotes (SMD=-0.3; 95% confidence interval [CI], -0.45 to -0.15; P<0.001). In subgroup analysis, we did not find statistically significant correlation between OPRM1 A118G polymorphism and opioid pain relief among Caucasian patients (SMD=-0.15; 95% CI, -0.29 to -0.00; P=0.04), as well as among morphine users (SMD =-0.20; 95% CI, -0.40 to 0.00, P=0.05), except for Asian patients (SMD=-0.42; 95% CI, -0.62 to -0.23; P<0.001). DISCUSSION: Our meta-analysis indicates that G allele (AG+GG) carriers of OPRM1 A118G polymorphism required more opioid analgesia in cancer pain management. The OPRM1 A118G polymorphism may help predict individuals' response to analgesia and achieve satisfactory cancer pain control.

Analysis of histone modifications at human ribosomal DNA in liver cancer cell.

Human liver cancer is the cancer commonly seen clinically. The transcription of ribosomal DNA (rDNA) is a critical step for cells, and epigenetic marks such as post-translational histone modifications have been involved in the regulation of rDNA transcription. But less is known about the pathogenesis of the liver cancers concerning the rDNA transcription regulation. Here we aligned the ChIP-seq data of histone modification markers and CTCF to the human genome assembly which contains a single rDNA repeat in human liver cancer cell and validated their distribution with ChIP-QPCR. Human liver cancer cell possesses a higher enrichment of H3K4me1 and H3K27me3 at ~28 kb within the intergenic spacer (IGS) of rDNA and a higher enrichment of H3K4me3 and H3K27ac upstream of TSS. Furtherly, we studied whether UBF could affect histone modification markers and CTCF at rDNA in human liver cancer cell. UBF depletion leads to a decrease of gene activation mark H3K4me3 across the rDNA promoter. And other histone modification marks and CTCF were not altered after UBF depletion. Taken together, our data showed a high resolution map of histone modification marks at rDNA in human liver cancer cell and provide novel evidence to decipher chromatin-mediated regulation of rDNA in liver cancer.