Anti-STAT3 (Phospho-Tyr705) Antibody (A50171)

Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in the world. The aim of the present study is to determine the antitumor effect of PF-04691502, a potent inhibitor of PI3K and mTOR kinases, on the apoptosis and angiogenesis of the hepatoma cancer cells. Our results indicate that treatment of cancer cells with PF-04691502 reduces cell viability and inhibits cell growth in a dose-dependent manner. PF-04691502 triggers apoptosis via a mitochondrial pathway, accompanied by activation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP). Pre-treatment of hepatoma cells with the caspase-3 inhibitor (z-DEVD-fmk) blocks the PF-04691502-induced death of these cells. In addition, growth factors-induced tube formation and the migration of HUVECs are markedly inhibited by PF-04691502 treatment. The mechanisms of anti-angiogenesis of PF-04691502 are associated with inhibiting the expression of VEGF and HIF-1α. Based on the overall results, we suggest that PF-04691502 reduces hepatocellular carcinoma cell viability, induces cell apoptosis, and inhibits cell growth and tumor angiogenesis, implicating its potential therapeutic value in the treatment of HCC.

In recent years, accumulating evidence suggests that atrial natriuretic peptide (ANP), a hormone widely known as a result of its significant effects on the cardiovascular system mediated by natriuretic peptide receptor A (NPRA), may play a nonnegligible role in the regulation of immune responses. In this study, we firstly investigated whether ANP signaling could regulate the differentiation and capacity of Th17 cells and discovered ANP-dose (10(-8)-10(-6)M) dependently indeed suppressed the differentiation of Th17 cells along with the reduced IL-17 production by polarizing naïve CD4(+) T cells isolated from splenocytes to Th17 phenotype in vitro. Moreover, ANP primarily signals through NPRA and cGMP-dependent protein kinase (PKG) which could be antagonized when pretreated with either ANP/NPRA signaling antagonist or PKG inhibitor. In addition, we also found that ANP signaling could upregulate the levels of phosphorylation of Akt which was hypothesized to be implicated in ANP-induced inhibition of Th17 development in our studies, and the effect of ANP on the development of murine Th17 cells seemed to be partially reversed when an inhibitor of phosphatidylinositol 3'-kinase (PI3K)/Akt had been performed in advance. Briefly, we showed for the first time that ANP signaling could suppress murine Th17 cell development from naïve CD4(+) T cells in vitro through NPRA/PKG pathway and the PI3K-Akt signal was implicated in the ANP-mediated suppression of Th17 development.

Lens epithelium-derived growth factor (LEDGF)/dense fine speckles 70  kDa protein (DFS70) is a transcription cofactor that enhances growth and is overexpressed in various cancers. In the epidermis, LEDGF/DFS70 localizes to the nucleus of keratinocytes (KCs) in the basal layers and to the cytoplasm of cells in the upper layers. However, the biological and pathological relevance of LEDGF/DFS70 in the epidermis is virtually unknown. Compared with normal epidermis, we detected strong nuclear staining of LEDGF/DFS70 in both the spinous and basal layers of the epidermis of psoriatic skin. To investigate the roles of LEDGF/DFS70 in the epidermis of psoriatic skin, we generated HaCaT cells that constitutively express enhanced green fluorescence protein (EGFP)-LEDGF (EGFP-LEDGF-HaCaT) or EGFP alone (EGFP-HaCaT) as a control. EGFP-LEDGF-HaCaT cells had increased expression of IL-6, which was attenuated by LEDGF-specific RNA interference and the p38-specific inhibitors SB-239063 and SB-203580. Furthermore, EGFP-LEDGF-HaCaT cells had increased expression of S100A7 and S100A9 and decreased expression of filaggrin. These findings are compatible with the expression pattern in psoriatic tissues. Taken together, these results strongly suggest that ectopic expression of LEDGF/DFS70 in KCs could be involved in the pathology of psoriasis vulgaris.

The effects of bisphenol A (BPA) on the differentiation of serum-free mouse embryo (SFME) cells, the astrocyte progenitor cells in the central nervous system, were examined. SFME cells were exposed to 10 ng/ml leukemia inhibitory factor (LIF) and 10ng/ml bone morphogenetic protein 2 (BMP2) to increase glial fibrillary acidic protein (GFAP) expression and induce cell differentiation. Various concentrations of BPA (0.1 pg/ml-1 microg/ml) were then added to determine their effects on the cell differentiation. SFME cells were effectively differentiated by LIF and BMP2 in completely serum-free cultures. Cell proliferation following cell differentiation was not significantly affected by low-level BPA. However, GFAP expression was significantly increased in SFME cells in the presence of 1-100 pg/ml BPA. These increases were due to excessive activation of signal transducer and activator of transcription 3 (STAT3) and mothers against decapentaplegic homolog 1 (Smad1) by the low-level BPA.