[Effect of Kv1.3 and KCa3.1 potassium ion channels on the proliferation and migration of monocytes/macrophages].

This study was aimed to investigate the effects of blockade of Ca(2+) activated channel KCa3.1 and voltage-gated potassium channel Kv1.3 of the monocytes/macrophages on inflammatory monocyte chemotaxis. Chemotaxis assay was used to test the inflammatory Ly-6C(hi) monocyte chemotaxis caused by the monocytes/macrophages. The proliferation of monocytes/macrophages was detected by cell counting kit-8 (CCK8). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the C-C motif ligand 7 (CCL7) in cultured media. The results showed that the recruitment of Ly-6C(hi) monocyte induced by monocytes/macrophages was suppressed by the potent Kv1.3 blocker Stichodactyla helianthus neurotoxin (ShK) or the specific KCa3.1 inhibitor TRAM-34. Meanwhile, the proliferation of monocytes/macrophages was significantly inhibited by ShK. The response of Ly-6C(hi) monocyte pretreated with ShK or TRAM-34 to CCL2 was declined. These results suggest that KCa3.1 and Kv1.3 may play an important role in monocytes/macrophages' proliferation and migration.

Blockade of KCa3.1 Attenuates Left Ventricular Remodeling after Experimental Myocardial Infarction.

BACKGROUND/AIMS: After myocardial infarction (MI), cardiac fibrosis greatly contributes to left ventricular remodeling and heart failure. The intermediate-conductance calcium-activated potassium Channel (KCa3.1) has been recently proposed as an attractive target of fibrosis. The present study aimed to detect the effects of KCa3.1 blockade on ventricular remodeling following MI and its potential mechanisms. METHODS: Myocardial expression of KCa3.1 was initially measured in a mouse MI model by Western blot and real time-polymerase chain reaction. Then after treatment with TRAM-34, a highly selective KCa3.1 blocker, heart function and fibrosis were evaluated by echocardiography, histology and immunohistochemistry. Furthermore, the role of KCa3.1 in neonatal mouse cardiac fibroblasts (CFs) stimulated by angiotensin II (Ang II) was tested. RESULTS: Myocardium expressed high level of KCa3.1 after MI. Pharmacological blockade of KCa3.1 channel improved heart function and reduced ventricular dilation and fibrosis. Besides, a lower prevalence of myofibroblasts was found in TRAM-34 treatment group. In vitro studies KCa3.1 was up regulated in CFs induced by Ang II and suppressed by its blocker.KCa3.1 pharmacological blockade attenuated CFs proliferation, differentiation and profibrogenic genes expression and may regulating through AKT and ERK1/2 pathways. CONCLUSION: Blockade of KCa3.1 is able to attenuate ventricular remodeling after MI through inhibiting the pro-fibrotic effects of CFs.

Fucoidan inhibits the growth of hepatocellular carcinoma independent of angiogenesis.

Some sulphated polysaccharides can bind bFGF but are unable to present bFGF to its high-affinity receptors. Fucoidan, a sulphated polysaccharide purified from brown algae, which has been used as an anticancer drug in traditional Chinese medicine for hundreds of years, exhibits a variety of anticancer effects, including the induction of the apoptosis and autophagy of cancer cells, the inhibition of the growth of cancer cells, the induction of angiogenesis, and the improvement of antitumour immunity. Our research shows that fucoidan dose not inhibit the expressions of VEGF, bFGF, IL-8, and heparanase in HCC cells and/or tumour tissues. Moreover, fucoidan exhibited low affinity for bFGF and could not block the binding of bFGF to heparan sulphated. Although fucoidan had no effect on angiogenesis and apoptosis in vivo, this drug significantly inhibited the tumour growth and the expression of PCNA. These results suggest that fucoidan exhibits an anticancer effect in vivo at least partly through inhibition of the proliferation of HCC cells, although it is unable to suppress the angiogenesis induced by HCC.

Gekko-sulfated glycopeptide inhibits tumor angiogenesis by targeting basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is a therapeutic target of anti-angiogenesis. Here, we report that a novel sulfated glycopeptide derived from Gekko swinhonis Guenther (GSPP), an anticancer drug in traditional Chinese medicine, inhibits tumor angiogenesis by targeting bFGF. GSPP significantly decreased the production of bFGF in hepatoma cells by suppressing early growth response-1. GSPP inhibited the release of bFGF from extracellular matrix by blocking heparanase enzymatic activity. Moreover, GSPP competitively inhibited bFGF binding to heparin/heparan sulfate via direct binding to bFGF. Importantly, GSPP abrogated the bFGF-stimulated proliferation and migration of endothelial cells, whereas it had no inhibitory effect on endothelial cells in the absence of bFGF. Further study revealed that GSPP prevented bFGF-induced neovascularization and inhibited tumor angiogenesis and tumor growth in a xenograft mouse model. These results demonstrate that GSPP inhibits tumor angiogenesis by blocking bFGF production, release from the extracellular matrix, and binding to its low affinity receptor, heparin/heparan sulfate.

[Expression and significance of macrophage migration inhibitory factor in gastric adenocarcinoma].

OBJECTIVE: To investigate the expression of MIF on the gastric adenocarcinoma, evaluate the relation between the MIF expression and tumor differentiation, lymph node metastasis and other clinical patho-features. METHODS: 120 gastric adenocarcinoma cancer tissues, 40 tissues besides cancer and 40 common mucosa tissues specimens are collected. Detect the expression of MIF with immunohistochemistry method (Streptavidin-Peroxidase). RESULTS: Positive rate of MIF expression in gastric cancer is 80.8% (97/120). Those in poorly differentiated, moderately differentiated and well-differentiated gastric adenocarcinoma are 97.5% (39/40), 82.5% (33/40), 62.5% (25/40), analytical factor of Spearman rank correlation r(s) is 0.458 (χ(2) = 27.046, P < 0.001). Positive rate of MIF expression in tissues besides cancer is 40% (16/40) and that in normal gastric mucosa is 7.5% (3/40). Positive rate of MIF expression in gastric adenocarcinoma without lymph node metastasis is 40% (22/55) and the rate with lymph node metastasis is 67% (44/65). CONCLUSIONS: There is overexpression of MIF in the gastric adenocarcinoma. Expression of MIF in different differentiated cancer is different. Expression in poorly differentiated is higher than that in moderately differentiated and well-differentiated cancer. The level of expression of MIF malignancy has positive correlation with malignancy degree of gastric adenocarcinoma. MIF expression has nothing to do with age, gender, tumor sizes or location.