Objective To investigate the relationship of STAT3 with expressions of MMP-2,MMP-9 and TIMP-1 and with epithelial-mesenchymal transition (EMT) in breast cancer cells,and to explore the clinical significances.Methods The mRNA of STAT3 and the protein expressions of pSTAT3,MMP-2,MMP-9 and TIMP-1 of breast cancer cells in 84 patients with breast cancer were determined by real-time RT-PCR technique and immunohistochemical method in paraffin-embedded specimensm respectively.Normal breast tissues adjacent to breast cancer were taken as controls.Results mRNA expression of STAT3 was significantly higher in breast cancer tissues than in controls (t=4.513,P＜ 0.001).Protein expressions of pSTAT3,MMP-2,MMP-9 and TIMP-1 were higher in breast cancer tissues than in controls (all P＜ 0.05).There were positive correlations between pSTAT3 expression and the expressions of MMP-2,MMP-9 and TIMP-1 in breast cancer tissues (all P＜0.05).The higher levels of pSTAT3 and MMP-2 were associated with poorer differentiation and more lymph node metastasis of breast cancer (both P＜0.05).The positive expression of MMP-9 was correlated with lymph node metastasis (P＜0.05),but not with histological grading (P＞0.05).The positive expression of TIMP-1 had no associations with histological grading and lymph node metastasis (both P＞0.05).There were no significant differences in the protein expressions level of pSTAT3,MMP-2,MMP-9 and TIMP-1 between different ages and different breast tumor sizes (all P＞0.05).Conclusions The increased expression of STAT3 in breast cancer cells is closely correlated with the increased expressions of MMP-2,MMP-9 and STAT3 inhibitor TIMP-1.The activation of STAT3 gene can mediate EMT by inducing the protein expressions of MMP-2,MMP-9,which promotes the invasion and metastasis of breast cancer.

The loss of endothelial connective integrity and endothelial barrier dysfunction can lead to increased vascular injury, which is related to the activation of endothelial inflammasomes. There are evidences that low concentrations of aspirin can effectively prevent cardiovascular diseases. We hypothesized that low-dose aspirin could ameliorate endothelial injury by inhibiting the activation of NLRP3 inflammasomes and ultimately prevent cardiovascular diseases. Microvascular endothelial cells were stimulated by lipopolysaccharide (2 μg/mL) and administrated by 0.1-2 mmol/L aspirin. The wild type mice were stimulated with LPS (100 μg/kg/day), and 1 h later treated with aspirin (12.5, 62.5, or 125 mg/kg/day) and dexamethasone (0.0182 mg/kg/day) for 7 days. Plasma and heart were harvested for measurement of ELISA and immunofluorescence analyses. We found that aspirin could inhibit NLRP3 inflammasome formation and activation in dose-dependent manner and has correlation between the NLRP3 inflammasome and the ROS/TXNIP pathway. We also found that low-concentration aspirin could inhibit the formation and activation of NLRP3 inflammasome and restore the expression of the endothelial tight junction protein zonula occludens-1/2 (ZO1/2). We assume that aspirin can ameliorate the endothelial layer dysfunction by suppressing the activation of NLRP3 inflammasome.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.