Overexpression of long non-coding RNA cancer susceptibility 11 is involved in the development of chemoresistance to carboplatin in hepatocellular carcinoma.

The long non-coding (lnc)RNA cancer susceptibility 11 (CASC11) promotes gastric cancer, however its role in other diseases is unknown. The present study demonstrated upregulation of lncRNA CASC11 and microRNA (miR)-21 in hepatocellular carcinoma (HCC). Furthermore, the expression of CASC11 was positively correlated with that of miR-21 in HCC tumors. Moreover, overexpression of lncRNA CASC11 led to upregulation of miR-21 in HCC cells, whereas overexpression of miR-21 had no effect on CASC11 levels. The levels of lncRNA CASC11 and miR-21 were found to be upregulated in the plasma of patients with HCC during chemotherapy. In vitro cell experiments demonstrated upregulation of lncRNA CASC11 in HCC cells treated with carboplatin. Additionally, overexpression of lncRNA CASC11 promoted, whereas its knockdown inhibited the viability of HCC cells following carboplatin treatment. Finally, overexpression of miR-21 ameliorated the effects of lncRNA CASC11 knockdown on cell viability. Thus, these findings suggest that upregulation of lncRNA CASC11 is involved in the development of chemoresistance to carboplatin in patients with HCC, via the upregulation of miR-21.

Association between NF-κB expression and drug resistance of liver cancer.

Association between the expression of nuclear factor κB (NF-κB) and the drug resistance of hepatoma cells was investigated. HepG-2 cells and HepG2/ADM cells were cultured, respectively. The morphology and status of the two groups of cells were observed by cell white light. The immunofluorescence by NF-κB and MDR1 staining on HepG-2 cells and HepG2/ADM cells, respectively, was applied and the fluorescence expression in the two groups of cells was observed. RT-qPCR was used to detect the expression of NF-κB and MDR1 mRNA, the NF-κB and MDR1 protein expression was detected by western blot analysis. The results of cell white illumination showed that the structure of HepG-2 and HepG2/ADM cells was complete and the cell morphology was normal, and there was no significant difference, and could be used for comparative study. Immunofluorescence staining showed that the expression of NF-κB and MDR1 in HepG-2 cells was very low, while the expression of NF-κB and MDR1 in HepG2/ADM cells was increased significantly. The RT-qPCR results showed that NF-κB and MDR1 mRNA expression in HepG-2 cells was very low, while NF-κB and MDR1 mRNA expression in HepG-2/ADM cells was significantly increased, and western blot results showed that NF-κB and MDR1 protein expression in HepG-2 cells was very low, while NF-κB and MDR1 protein expression in HepG-2/ADM cells was increased significantly. The results of variance analysis showed that there was significant difference in the expression of the control group and paeonol group (P<0.01). In conclusion, the expression of NF-κB in the drug-resistant cells of liver cancer is closely related to the resistance-related gene MDR1. This result may provide a new solution for the drug resistance of liver cancer.

Astragaloside IV combating liver cirrhosis through the PI3K/Akt/mTOR signaling pathway.

Astragaloside IV (AS-IV) in improving liver cirrhosis injury in rats and its effect on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) signaling pathway were observed. Rat model of liver cirrhosis was induced by injection of carbon tetrachloride (CCl4). A total of 36 Sprague-Dawley (SD) rats were randomly divided into three groups: the normal control group (n=10), the model control group (n=13), and the AS-IV group (n=13). The normal control group was injected with olive oil and given carboxymethyl cellulose (CMC)-Na (10 ml/kg/day), the model control group was given CMC-Na (10 ml/kg/day), and the AS-IV group underwent intragastric administration of AS-IV (20 ml/kg/day). The content of alanine transaminase (ALT) and aspartate transaminase (AST) of rats was detected. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß in serum were detected via enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was applied to observe morphological changes in liver tissues. The expression of collagens in liver tissues was detected via Masson's trichrome staining. Additionally, the expression of proteins in liver tissues was detected via western blotting. Compared with those in the blank group, the levels of AST, ALT, TNF-α, IL-6 and IL-1ß were higher, the expression level of collagens in liver tissues was increased, and the expression ratios of phosphorylated (p)-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR proteins were increased in the model group. Compared with the model group, AS-IV could significantly decrease the content of AST, ALT, TNF-α, IL-6 and IL-ß in serum of rats, obviously inhibit the expression of collagens in liver tissues and decrease the expression ratios of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR proteins in liver tissues. AS-IV can inhibit the inflammatory response so as to reduce the expression of collagens, and its mechanism may play a key role by inhibiting the PI3K/Akt/mTOR signaling pathway.