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Gambogic acid inhibits TNF-?-induced invasion of human prostate cancer PC3 cells in vitro through PI3K/Akt and NF-?B signaling pathways.

ABSTRACT: To investigate the mechanisms underlying the inhibitory effect of gambogic acid (GA) on TNF-?-induced metastasis of human prostate cancer PC3 cells in vitro.TNF-?-mediated migration and invasion of PC3 cells was examined using migration and invasion assays, respectively. NF-?B transcriptional activity and nuclear translocation were analyzed with luciferase reporter gene assays, immunofluorescence assays and Western blots. The ability of p65 to bind the promoter of Snail, an important mesenchymal molecular marker, was detected using a chromatin immunoprecipitation (ChIP) assay. After treatment with Snail-specific siRNA, the expression of invasiveness-associated genes was measured using quantitative real-time PCR and Western blot.GA significantly inhibited the viability of PC3 cells at 1-5 ?mol/L, but did not produce cytotoxic effect at the concentrations below 0.5 ?mol/L. GA (0.125-0.5 ?mol/L) dose-dependently inhibited the migration and invasion of PC3 cells induced by TNF-? (10 ng/mL). Moreover, the TNF-?-mediated activation of phosphatidylinositol-3-OH kinase/protein kinase B (PI3K/Akt) and NF-?B pathways was suppressed by GA (0.5 ?mol/L). Furthermore, this anti-invasion effect of GA was associated with regulation of Snail. Snail expression was significantly down-regulated by treatment with GA (0.5 ?mol/L) in the TNF-?-stimulated PC3 cells.GA inhibits TNF-?-induced invasion of PC3 cells via inactivation of the PI3K/Akt and NF-?B signaling pathways, which may offer a novel approach for the treatment of human prostate cancer.

SUBMITTER: Lu L

PROVIDER: S-EPMC4003358 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Gambogic acid inhibits TNF-α-induced invasion of human prostate cancer PC3 cells in vitro through PI3K/Akt and NF-κB signaling pathways.

Lü Lei L Tang Dong D Wang Liang L Huang Lu-qi LQ Jiang Guo-song GS Xiao Xing-yuan XY Zeng Fu-qing FQ

Acta pharmacologica Sinica 20120319 4

<h4>Aim</h4>To investigate the mechanisms underlying the inhibitory effect of gambogic acid (GA) on TNF-α-induced metastasis of human prostate cancer PC3 cells in vitro.<h4>Methods</h4>TNF-α-mediated migration and invasion of PC3 cells was examined using migration and invasion assays, respectively. NF-κB transcriptional activity and nuclear translocation were analyzed with luciferase reporter gene assays, immunofluorescence assays and Western blots. The ability of p65 to bind the promoter of Sna ...[more]

PMID: 22426696

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Project description:[Aim] EBVaGC accounts for about 10% of gastric cancer and has a better prognosis than EBVnGC, but its molecular mechanism is still unclear. We investigated the role of EBV-miR-BART1-3p in the occurrence and development of EBVaGC by applying bioinformatics methods, high-throughput sequencing, in vitro experiments, target gene screening and verification, differential gene protein interaction network and gene regulatory network construction. [Materials and Methods] The data set GSE51575 was normalized, and the outlier samples were deleted. Finally, gene expression profiles of 11 EBVaGC and 14 EBVnGC tumor tissues and non-tumor control tissues were obtained. Differential gene function analysis was performed, and molecular regulatory network was constructed. The mRNA expression levels of SNU-719 (EBV-positive gastric cancer cell line), AGS, AGS-NC (EBV-negative gastric cancer cell line) and AGS-OE (lentivirus-transfected miR-BART1-3p overexpression cell line) were detected by high-throughput next-generation sequencing technology, and differential gene expression characteristics were analyzed. To investigate the effect of miR-BART1-3p overexpression on mRNA expression level of gastric cancer cells and construct the protein interaction network of differential genes and the regulatory network of miR-BART1-3p gene. DIANA-MR micro-T, miRnada, miRDB, TarBase v.8, and ViRBase online databases were used to predict the target genes of miR-BART1-3p and GO enrichment analysis of target gene function was performed. Real-time fluorescence quantitative PCR was used to detect the expression levels of miR-BART1-3p and target genes in SNU719, AGS-OE and AGS gastric cancer cells. The effects of overexpression of EBV-miR-BART1-3p on proliferation, apoptosis, invasion, and migration of gastric cancer cells were investigated by CCK-8, cell cloning, cell scratch and Transwell. [Results] By analyzing the gene expression profile of the GSE51575 dataset, we found that EBVaGC up-regulated the expression of immune cell membrane protein receptors and chemokine family, and was involved in inducing tumor immunity, suggesting a better prognosis. EBVnGC significantly up-regulated the expression of AURK, BUB1B, CCNA2 and CDC20, suggesting the risk of malignant progression and recurrence. High-throughput next-generation sequencing of SNU719 and AGS to detect differences in gene expression revealed that EBVaGC cells (SNU719) up-regulated the expression of genes that inhibit malignant progression as well as potential tumor immunotherapy targets. These results are consistent with those found in the GSE51575 dataset. Fifteen miR-BART1-3p target genes, including FAM168A, TET3, HBP1, ZBTB5, ATXN7L3, KMT5C, SPARC and BMF, were predicted and screened by online tools. After the overexpression of miR-BART1-3p in AGC(EBVnGC) cells, the proliferation, migration, and invasion ability were significantly inhibited, and the signaling pathway promoting tumor progression was also limited in activation. [Conclusions] The overexpression of miR-BART1-3p may inhibit the proliferation and invasion and migration of gastric cancer cells by inhibiting the activation of STAT3/ pSTAT3 and PI3K/AKT signaling pathways and may become a target for the treatment of EBVaGC, which is worthy of further study.

Dataset Information

Gambogic acid inhibits TNF-?-induced invasion of human prostate cancer PC3 cells in vitro through PI3K/Akt and NF-?B signaling pathways.

Publications

Gambogic acid inhibits TNF-α-induced invasion of human prostate cancer PC3 cells in vitro through PI3K/Akt and NF-κB signaling pathways.

Similar Datasets

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