The present study aimed to determine the effects and mechanism of ChaC glutathione specific γ‑glutamylcyclotransferase 1 (CHAC1) on cell viability and the sensitivity of prostate cancer cells to docetaxel. Compared with non‑tumor human prostate epithelial RWPE‑1 cells, the mRNA and protein levels of CHAC1 significantly decreased in two prostate cancer cell lines, DU145 and 22RV1, as measured by quantitative polymerase chain reaction and western blot analysis (P<0.05). The cell viability and glutathione (GSH) levels were significantly inhibited in prostate cancer cells following overexpression of CHAC1 (P<0.01), while they were significantly increased in DU145 cells transfected with CHAC1 siRNA (P0.05). The expression levels of several endoplasmic reticulum (ER) stress‑related factors were then measured by western blot analysis. Following transfection with plasmid overexpressing CHAC1, ER markers, BIP and CHOP levels, were significantly upregulated (P<0.01), while GSH co‑treatment decreased this upregulation. In addition, CHAC1 protein levels were significantly upregulated in cells treated with a ferroptosis activator (P<0.05). A liperflo reagent was then used to determine intracellular lipid peroxide levels. The intracellular lipid peroxides levels were significantly increased following CHAC1‑overexpression (P<0.05), while GPX4 protein levels were significantly decreased (P<0.01). The cell viability was significantly inhibited (P0.05). This inhibition was also eliminated following the addition of a ferroptosis inhibitor. In summary, CHAC1 may inhibit cell viability and increase the sensitivity of prostate cancer cells to DTX. The cellular mechanism may involve the induction of ER stress and ferroptosis. The results of the present study identified a potentially novel therapeutic target for prostate cancer, which may be useful in patients with castration‑resistant prostate cancer.

The aim of the present study was to investigate the role of prolyl 4-hydroxylase beta polypeptide (P4HB) in the chemoresistance of liver cancer. Drug‑resistant liver cancer cell lines, such as HepG2/adriamycin (ADR) cells, were treated and screened using adriamycin. Gene interference was used to silence the expression of P4HB in liver cancer cells. Cell viability, invasiveness and migration were assessed using CCK8, Transwell and wound healing assays, respectively. In addition, changes to key genes and proteins in the epithelial‑mesenchymal transition (EMT) and β‑catenin/Snail pathway were analyzed using reverse transcription‑quantitative PCR and western blotting. Drug‑resistant HepG2/ADR cells were successfully cultivated; the IC50 to ADR for HepG2/ADR and HepG2 cell lines was 4.85 and 0.61 µM, respectively. HepG2/ADR cells exhibited higher invasion and migration abilities compared with HepG2 cells (P<0.05). E‑cadherin mRNA and protein expression levels in HepG2/ADR cells were decreased significantly, whereas P4HB, N‑cadherin and vimentin mRNA and protein levels were significantly increased compared with HepG2 cells (all P<0.05). Knockdown of P4HB significantly decreased cell viability and the invasion and migration ability of HepG2/ADR cells. In addition, P4HB knockdown enhanced E‑cadherin mRNA and protein expression levels, whereas N‑cadherin, vimentin, total β‑catenin, nuclear β‑catenin and Snail mRNA and protein levels were significantly decreased (all P<0.05). Overall, the present study demonstrated that EMT and β‑catenin/Snail pathway influence P4HB modulation in liver cancer chemoresistance.

Huangqi decoction (HQD) is used for liver fibrosis and cirrhosis treatment in Chinese medicine. This study aims to investigate the pharmacological actions of HQD against liver fibrosis in rats by high-throughput gene expression profiling, network analysis and real-time qRT-PCR. We analyzed the profiles of differentially expressed genes (DEGs) in dimethylnitrosamine (DMN)-induced liver fibrosis in rat. The liver tissue samples of control group (n = 3), model group (n = 3) and HQD group (n = 3) were examined by microarrays. Pathways were analyzed by KEGG. Pathway-gene and protein–protein interaction (PPI) networks were constructed with Cytoscape software. The expression of candidate genes was verified by qRT-PCR. P values less than 0.05 indicated statistical significance. Collagen deposition and hydroxyproline (Hyp) content were decreased in the HQD group compared with the model group (P < 0.001), while that of Hyp in the model group were increased compared with the control group (P < 0.001). In comparison with the model group, 1085 DEGs (all P < 0.05, |fold change| >1.5) and 52 pathways in the HQD group were identified. TGF-beta, ECM-receptor interaction, and the cell adhesion molecules pathways were significantly recovered by HQD (P < 0.001). A pathway-gene network was constructed, including 303 DEGs and 52 pathways, and 514 nodes and 2602 edges, among 142 genes with node degrees greater than 10. The expressions of PDGFra, PDGFrb, PDGFb, PDGFd, COL1A1, COL1A2, COL5A2, and THBS1 were significantly down-regulated by HQD (P < 0.001). HQD down-regulated the expressions of PDGFra, PDGFrb, PDGFb, PDGFd, COL1A1, COL1A2, COL5A2 and THBS1, and TGF-β and PDGF signaling pathways in the DMN-induced liver fibrosis in rats.

Background and Objective: GINS complex subunit 2 (GINS2), a member of the GINS complex, is involved in DNA replication. GINS2 is upregulated in a variety of aggressive tumors, such as leukemia, breast cancer, and cervical cancer. However, the role of GINS2 in pancreatic cancer has still remained elusive. In this study, PANC-1 and BxPC-3 cell lines were chosen to perform experiments in vitro. Additionally, the effects of GINS2 interference on the cell viability, cell apoptosis, cell cycle, and tumor growth in nude mice were analyzed.