The Association of Serum IL-33 and sST2 with Breast Cancer.

Breast cancer is one of the most common malignant diseases in women. The main cause of death from breast cancer is its metastases at distant sites in the body. Interleukin-33 (IL-33) is a cytokine of the IL-1 family and found overexpressed in various cancers. The aim of the present study was to explore the association of serum IL-33 and sST2 with breast cancer. Here, the serum levels of Interleukin-33 (IL-33) and sST2 were found significantly higher in breast cancer patients than in healthy volunteers. Serum levels of vascular endothelial growth factor (VEGF), metalloproteinase-11 (MMP-11), and platelet-derived growth factor-C (PDGF-C) were also greater in breast cancer patients compared to healthy volunteers. We found that serum levels of IL-33 or sST2 were positively correlated with the serum levels of VEGF, MMP-11, and PDGF-C. Moreover, breast cancer dataset downloaded from The Cancer Genome Atlas showed that patients with higher level of MMP-11 or PDGF-C expression had shorter survival time than those with lower level of these proteins. In conclusion, IL-33 and sST2 may serve as noninvasive diagnosis markers for breast cancer. IL-33 and sST2 were significantly associated with MMP-11 or PDGF-C which indicated poor prognosis of breast cancer patients.

Inhibitory effects of 2,3,4',5-tetrahydroxystilbene-2-O-ß-D-glucoside on angiotensin II-induced proliferation of vascular smooth muscle cells.

OBJECTIVE: To investigate the effect of 2,3,4',5-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG), an active component extracted from the root of Polygonum multiflorum, on angiotensin II (Ang II)-induced proliferation of cultured rat vascular smooth muscle cells (VSMCs) and to identify the potential mechanism. METHODS: Cell proliferation and cell cycle were determined by cell counting, 5-bromo-2'-deoxyuridine incorporation assay, proliferating cell nuclear antigen protein expression and flow cytometry. Levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), mitogenic extracellular kinase 1/2 (MEK1/2) and Src in VSMCs were measured by Western blot. The expression of c-fos, c-jun and c-myc mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR). Intracellular reactive oxygen species (ROS) was measured by fluorescence assay. RESULTS: TSG significantly inhibited Ang II-induced VSMCs proliferation and arrested cells in the G /S checkpoint (P<0.05 or P<0.01). TSG decreased the levels of phosphorylated ERK1/2, MEK1/2 and Src in VSMCs (P<0.05 or P<0.01). TSG also suppressed c-fos, c-jun and c-myc mRNA expression <0.05 or P<0.01). In addition, the intracellular ROS was reduced by TSG (P<0.01). CONCLUSIONS: TSG inhibited Ang II-induced VSMCs proliferation. Its antiproliferative effect might be associated with down-regulation of intracellular ROS, followed by the suppression of the Src-MEK1/2-ERK1/2 signal pathway, and hence, blocking cell cycle progression.

SCYL1BP1 has tumor-suppressive functions in human lung squamous carcinoma cells by regulating degradation of MDM2.

SCY1-like 1-binding protein 1 (SCYL1BP1) is a newly identified transcriptional activator domain containing protein with many unknown biological functions. Recently emerging evidence has revealed that it is a novel regulator of the p53 pathway, which is very important for the development of human cancer. However, the effects of SCYL1BP1 on human lung squamous carcinoma cell biological behavior remain poorly understood. In this study, we present evidence that SCYL1BP1 can promote the degradation of MDM2 protein and further inhibit the G1/S transition of lung squamous carcinoma cell lines. Functional assays found that reintroduction of SCYL1BP1 into lung squamous carcinoma cell lines significantly inhibited cell proliferation, migration, invasion and tumor formation in nude mice, suggesting strong tumor suppressive function of SCYL1BP1 in lung squamous carcinoma. Taken together, our data suggest that the interaction of SCYL1BP1/MDM2 could accelerate MDM2 degradation, and may function as an important tumor suppressor in lung squamous carcinomas.

The effect of 2,3,4',5-tetrahydroxystilbene-2-0-ß-D glucoside on neointima formation in a rat artery balloon injury model and its possible mechanisms.

2,3,4',5-tetrahydroxystilbene-2-0-ß-D glucoside (TSG) has been recognized to suppress the proliferation of vascular smooth muscle cells (VSMCs). The aim of the present study was to determine whether TSG inhibits neointimal hyperplasia in a rat carotid arterial balloon injury model. Balloon injury was induced in the left common carotid artery of rats. TSG (30, 60, 120 mg/kg/day) was treated from 3 days prior to, until 14 days after the induction of balloon injury. The ratio of intima-to-media was significantly reduced in the TSG-treated rats at 14 days after the induction of injury, which was associated with reduced expressions of proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (α-SMA) and platelet-derived growth factor-BB (PDGF-BB), as markers of VSMCs proliferation and migration. Additionally, TSG significantly inhibited PDGF-BB induced cell migration in cultured VSMCs. Furthermore, we explored the underlying mechanisms for such effects of TSG. The result showed that TSG markedly reduced balloon injury-induced AKT, extracellular signal-regulated kinase (ERK1/2) and nuclear factor kappaB (NF-κB) activation as well as mRNA expressions of c-myc, c-fos and c-jun, which is important signal pathway for VSMCs proliferation. And in both vivo and vitro model, TSG markedly regulated matrix metalloproteinase-2, 9 expressions and collagen I, III expressions, which are key factors in extracellular matrix for VSMCs migration. These results suggest that the anti-proliferative and anti-migrative effects of TSG on VSMCs could help to explain the beneficial effects of TSG on neointima hyperplasia induced by balloon injury.