Gene expression alterations of human liver cancer cells following borax exposure.

Borax is a boron compound that is becoming widely recognized for its biological effects, including lipid peroxidation, cytotoxicity, genotoxicity, antioxidant activity and potential therapeutic benefits. However, it remains unknown whether exposure of human liver cancer (HepG2) cells to borax affects the gene expression of these cells. HepG2 cells were treated with 4 mM borax for either 2 or 24 h. Gene expression analysis was performed using Affymetrix GeneChip Human Gene 2.0 ST Arrays, which was followed by gene ontology analysis and pathway analysis. The clustering result was validated using reverse transcription­quantitative polymerase chain reaction. A cell proliferation assay was performed using Celigo Image Cytometer Instrumentation. Following this, 2­ or 24­h exposure to borax significantly altered the expression level of a number of genes in HepG2 cells, specifically 530 genes (384 upregulated and 146 downregulated) or 1,763 genes (1,044 upregulated and 719 downregulated) compared with the control group, respectively (≥2­fold; P<0.05). Twenty downregulated genes were abundantly expressed in HepG2 cells under normal conditions. Furthermore, the growth of HepG2 cells was inhibited through the downregulation of PRUNE1, NBPF1, PPcaspase­1, UPF2 and MBTPS1 (≥1.5­fold, P<0.05). The dysregulated genes potentially serve important roles in various biological processes, including the inflammation response, stress response, cellular growth, proliferation, apoptosis and tumorigenesis/oncolysis.

[Effects of Epihopin on Proliferation and Apoptosis of KG-1a cells and Its Related Mechanism].

OBJECTIVE: To explore the possible mechanism underlaying interference of epihopin on the proliferation of AML KG-1a cells by inhibiting the Wnt/ß-catenin signaling pathway, so as to prvide the experimental basis for development of drug to treat the AML. METHODS: A total of 50 c57BL/6 mice were randomy divided into 5 group:blank control, model control, high, medium and low dose of epihopin. Except the blank control group, the KG-1a cells were injected in abdominal cavity of 4 groups for the establishment of model. The mice in high, middle and low dose groups were injected intramuscularly with 80, 40 and 20 mg/kg of epihopin respectively, while the mice in blank control and model control group were injected intramuscularly with saline. The Western blot was used to detect the expression of S phase kinase-related protein 2(SKP-2), ß-catenin, E-cadherin and poly-(ADP ribose) polymerase (PARP); the spectrophotometry was used to detect the activity of caspase 3 and procaspase-3, the flow cytometry was used to detect the cell cycle distribution and the apoptotic rate of KG-1a cells treated with epihopin. RESULTS: The epihopin could enhance the activity of caspase 3, decrease the level of procaspase 3; also could up-regulate the expression of E-acadherin and down-regulate the expression of SKP-2 and ß-catenin; and could increase the expression of PARP in dose-dependent manner. After KG-1a cels were treated with epihopin, the apoptosis rate of cells significantly increased, the KG-1a cells were arrested in G0/G1 phase, therefore the growth of KG-1a cells was significantly inhibited. CONCLUSION: The epihopin can dose-dependently split PARP to induce the apoptosis of KG-1a cells, its mechanism may relate with inhibition of Wnt/ß-catenin signaling pathway and its down-stream-related gene expression.