RESUMO
Purpurogallin carboxylic acid (PCA) is a natural phenol compound derived from Macleaya microcarpa (Maxim.) Fedde, which exerts particular antioxidant and anti-inflammatory capacities. However, the effects and mechanisms of PCA on liver cancer cells remain unknown. Therefore, network pharmacology and computer virtual docking were used to identify the target-proteins of PCA. In addition, surface plasmon resonance, protease activity and rhodamine excretion assays were carried out to evaluate the effects of PCA on the activity of ATP binding cassette subfamily G member 2 (ABCG2). The synergistic effects of PCA and 5-fluorouracil (5-FU) on liver cancer cell proliferation, cell cycle arrest, colony formation and spheroid formation abilities in vitro were determined by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, western blot analysis, colony formation and spheroid formation assays, respectively. ABCG2 was identified as a potential target of PCA, with a high docking score. The equilibrium dissociation constant of PCA for ABCG2 protein was 1.84 µM, while the median inhibitory concentration of this protein was 3.09 µM. In addition, the results demonstrated that PCA could significantly reduce the drug efflux capacity of liver cancer cells. CCK-8 assays revealed that liver cancer cell treatment with 10 µM PCA and 10 µM 5-FU exhibited the most potent synergistic effects on liver cancer cell proliferation at 48 h. Additionally, cell co-treatment with PCA and 5-FU also significantly attenuated the colony and spheroid formation abilities of liver cancer cells in vitro, while it promoted their arrest at the G1 phase of the cell cycle. Furthermore, ABCG2 silencing in liver cancer cells notably abrogated the synergistic effects of PCA and 5-FU. In conclusion, the present study demonstrated that PCA exhibited synergistic effects with 5-FU on liver cancer cells in vitro via targeting ABCG2. Therefore, PCA combined with 5-FU may be a potential strategy for liver cancer therapy.
RESUMO
Background: Atrial fibrillation (AF) is a very common clinical arrhythmia, accompanied by the overproliferation of cardiac fibroblasts (CFs). This study aimed to investigate the role of the long non-coding RNA(lncRNA) taurine upregulated gene 1 (TUG1) in the proliferation of CFs and further investigated its underlying mechanism. Methods: One hundred four paroxysmal AF patients and 94 healthy controls were recruited. Human cardiac fibroblasts (HCFs) were applied to establish an AF cell model through treatment with angiotensin II (AngII). qRT-PCR was used for the measurement of gene levels. The cell proliferation was detected by cell counting kit-8 (CCK-8). Luciferase reporter assay was performed for target gene analysis. Results: Elevated levels of TUG1 and low expression of miR-29b-3p were detected in the serum of AF patients compared with the healthy controls. Pearson's correlation analysis exhibited an inverse relationship between TUG1 and miR-29b-3p expression in AF patients (r = -7.106, p < 0.001). Knockdown of TUG1 inhibited AngII-induced CF proliferation. Taurine upregulated gene 1 (TUG1) functions as a competing endogenous RNA (ceRNA) for miR-29b-3p, and downregulation of miR-29b-3p reversed the role of TUG1 in CF proliferation. TGF-ß1 is a direct target gene of miR-29b-3p. Conclusions: Long non-coding RNA taurine upregulated gene 1 is a key regulator in the occurrence of AF. Slicing TUG1 inhibits CF proliferation by regulating the miR-29b-3p/TGF-ß1 axis.
RESUMO
PURPOSE: To observe the clinical effect of radical resection combined with antiviral therapy in patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), and to analyze the risk factors affecting its prognosis. METHODS: The clinical data of 132 patients with HBV-associated HCC treated in our hospital from January 2015 to December 2016 were retrospectively analyzed, and the patients were randomly divided into Control group (n=66) and Anti-virus group (n=66). The changes in liver function indexes, HBV-deoxyribonucleic acid (DNA) load and alpha fetoprotein (AFP) level were compared between the two groups before and after treatment. The tumor recurrence and patients' survival were recorded during the follow-up period, and the possible influencing factors for the prognosis of patients with HBV-associated HCC were analyzed. RESULTS: After treatment, the levels of alanine aminotransferase (ALT), albumin (ALB), prealbumin (PA) and AFP significantly declined in both groups (p<0.05), while the levels of ALT, PA and AFP were significantly lower in Anti-virus group than those in Control group (p<0.001). After treatment, the HBV-DNA level declined in both groups compared with that before treatment, while it was obviously lower in Anti-virus group than that in Control group (p<0.001). During treatment, the total incidence rate of complications in Anti-virus group was 37.9%, markedly lower than that in Control group 59.1% (p=0.023). The results of log-rank test showed that both OS and PFS rates were far higher in Anti-virus group than those in Control group (p=0.043, p=0.034). The results of Cox multivariate analysis revealed that a low degree of tumor histological differentiation, a large diameter of tumor and no antiviral therapy were independent risk factors affecting the OS rate of patients after treatment (p=0.030, p=0.017). CONCLUSIONS: Antiviral therapy after radical resection of HBV-associated HCC can effectively inhibit the replication of HBV, reduce the recurrence rate of tumor, and prolong the OS of patients. Low grade of tumor histological differentiation, large diameter of tumor and no antiviral therapy are independent risk factors affecting the OS rate of patients after treatment.