• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.193-201
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• 2018

Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs. Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.

• Korean Journal of Acupuncture
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• v.30 no.4
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• pp.212-219
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• 2013

Objectives : Cirsium japonicum is a traditional Korean medicine that has been used in the treatment of inflammatory diseases such as appendicitis, hepatitis, pulmonary abscess and tumor. The aim of study was to elucidate anti-migratory activity of CJP(Cirsium japonicum pharmacopuncture) through regulation of inflammatory mediators in C6 glioma cell. Methods : Nitric oxide(NO) production was determined by using nitrite assay. The cell migration was analyzed by wound-healing assay and Boyden chamber assay. The expression levels of iNOS, and protein kinase C(PKC)-${\alpha}$ were measured by western blotting assay. Results : CJP showed a significant decrease on NO production. Moreover, glioma cell migration was effectively suppressed by CJP. Furthermore, CJP inhibited the expressions of iNOS and PKC-${\alpha}$ in C6 glioma cells. Conclusions : These results suggest that CJP inhibits glioma cell migration and iNOS expression through regulation of PKC-${\alpha}$. Therefore, it is expected that CJP could be an effective agents for blocking malignant progression of glioma.

• Journal of the Korean Society of Visualization
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• v.18 no.2
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• pp.10-17
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• 2020

The curvature of wound boundaries has been identified as a key modulator that determines a type of force responsible for cell migration. While several studies report how certain curvatures of the boundary correlate with the rate at which the wound closes, it remains unclear how these curvatures are spatiotemporally formed to regulate the healing process. We investigated the dynamic changes in the boundary curvatures by visualizing cell migration patterns. Locally, cells at the convex boundary continuously move forward with transmitting kinetic responses behind to the cells away from the boundary, and cells at the concave boundary exhibit dramatic contracting motion, like a purse-string, when they accumulate enough negative curvatures to gain the thrust toward the void. Globally, the dynamics of boundary geometries are controlled by the diffusive flow of cells driven by the density gradient between the wound area and the cell layer.

• BMB Reports
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• v.41 no.12
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• pp.858-862
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• 2008

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a zinc-dependent proteinase found in cholesterol-rich lipid rafts on the plasma membrane. MT1-MMP hydrolyzes extracellular matrix (ECM) proteins, activates pro-matrix metalloproteinase-2 (proMMP-2) and plays an important role in ECM remodeling, cancer cell migration and metastasis. The role of caveolin-1, an integral protein of caveolae, in the activation of MT1-MMP remains largely unknown. Here, we show that the expression of caveolin-1 attenuates the activation of proMMP-2, reduces proteolytic cleavage of ECM and inhibits cell migration. We utilized the cytoplasmic tail domain deletion (${\Delta}CT$) or the E240A mutant of MT1-MMP. Co-expression of caveolin-1 with the wild-type or the ${\Delta}CT$ MT1-MMP decreased the proMMP-2 activation and inhibited collagen degradation and cell migration. Caveolin-1 had no effect on the catalytically inert E240A MT1-MMP. Our findings suggest that caveolin-1 is essential in the down-regulation of MT1-MMP activity by promoting internalization from the cell surface.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.326.2-327
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• 2002

Glial cell-derived neurotrophic factor (GDNF) is a potent neurotrophic factor that enhances survival of midbrain doparminergic neuron. GDNF and its receptors are widely distributed in brain and are believed to be involved in the control of neuron survival and differentiation. In this study, we examined the effect of GDNF on proliferation and migration of Hs683 human glioma cells. GDNF markedly enhances proliferation and migration of Hs683 cells in a dose-dependent manner. (omitted)

• 한국전산유체공학회:학술대회논문집
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• 2010.05a
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• pp.556-561
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• 2010

This paper proposes a three-dimensional haptotaxis model to simulate the migration of the population of cancer cells. The invasion of the cancer cells relates with the hapto- and the effect of the energy between cells and (ECM). The diffuse interface model is employed, which incorporates haptotaxis mechanism and interface energies. The semi-implicit Fourier spectral scheme is adopted for efficient complications. The simulation results reveal rich dynamics of cancer cells migration.

• Biotechnology and Bioprocess Engineering:BBE
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• v.11 no.5
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• pp.402-407
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• 2006

Vascular endothelial cells release proteinases that degrade the extracellular matrix (ECM), thus enabling cell migration during angiogenesis and vasculogenesis. Sildenafil citrate stimulates the nitric oxide-cyclic guanosine monophosphate pathway through inhibition of phosphodiesterase type V (PDE5). In this report, we examined the mechanisms underlying sildenafil citrate-induced cell migration using cultured mouse aortic endothelial cells (MAECs). Sildenafil citrate induced migration and proteinase secretion by murine endothelial cells. Sildenafil citrate induced the secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9, which is inhibited by $NF-{\kappa}B$ inhibitors. Sildenafil citrate also induced the secretion of plasmin, which is inhibited by PI 3'-kinase inhibitors. It is suggested that sildenafil citrate-induced migrating activity in endothelial cells may be accomplished by increased secretion of proteinases.

• Nutrition Research and Practice
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• v.14 no.2
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• pp.127-133
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• 2020

BACKGROUND/OBJECTIVES: Non-small cell lung cancer is mostly recognized among other types of lung cancer with a poor prognosis by cause of chemotherapeutic resistance and increased metastasis. Luteolin has been found to decrease cell metastasis. However, its underlying mechanisms remain unresolved. The objective of this study was to examine the effect (and its mechanism) of luteolin on the migration and invasion of human non-small cell lung cancer A549 cells. MATERIALS/METHODS: Cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Wound healing and transwell assays were evaluated to assess migration and invasion, respectively. Western blot analysis and immunofluorescence were further performed to investigate the role of luteolin and its mechanisms of action. RESULTS: Administration with up to 40 μM luteolin showed no cytotoxic activity on lung cancer A549 cells or non-cancer MRC-5 cells. Additionally, luteolin at 20-40 μM significantly suppressed A549 cells' migration, invasion, and the formation of filopodia in a concentration-dependent manner at 24 h. This is similar with western blot analysis, which revealed diminished the phosphorylated focal adhesion kinase (pFAK), phosphorylated non-receptor tyrosine kinase (pSrc), Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division control protein 42 (Cdc42), and Ras homolog gene family member A (RhoA) expression levels. CONCLUSIONS: Overall, our data indicate that luteolin plays a role in controlling lung cancer cells' migration and invasion via Src/FAK and its downstream Rac1, Cdc42, and RhoA pathways. Luteolin might be considered a promising candidate for suppressing invasion and metastasis of lung cancer cells.

• Journal of Gastric Cancer
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• v.20 no.1
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• pp.95-105
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• 2020

Purpose: Gastric cancer is a highly metastatic malignant tumor, often characterized by chemoresistance and high mortality. In the present study, we aimed to investigate the role of B-cell lymphoma 3 (Bcl-3) protein on cell migration and chemosensitivity of gastric cancer. Materials and Methods: The gastric cancer cell lines, AGS and NCI-N87, were used for the in vitro studies and the in vivo studies were performed using BALB/c nude mice. Western blotting, wound healing assay, Cell Counting Kit-8 assay, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to evaluate the role of Bcl-3 in gastric cancer. Results: We found that the protein expression of hypoxia (HYP)-inducible factor-1α and Bcl-3 were markedly upregulated under hypoxic conditions in both AGS and NCI-N87 cells in a time-dependent manner. Interestingly, small interfering RNA-mediated knockdown of Bcl-3 expression affected the migration and chemosensitivity of the gastric cancer cells. AGS and NCI-N87 cells transfected with si-RNA-Bcl-3 (si-Bcl-3) showed significantly reduced migratory ability and increased chemosensitivity to oxaliplatin, 5-fluorouracil, and irinotecan. In addition, si-Bcl-3 restored the autophagy induced by HYP. Further, the protective role of si-Bcl-3 on the gastric cancer cells could be reversed by the autophagy inducer, rapamycin. Importantly, the in vivo xenograft tumor experiments showed similar results. Conclusions: Our present study reveals that Bcl-3 knockdown inhibits cell migration and chemoresistance of gastric cancer cells through restoring HYP-induced autophagy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7687-7692
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• 2014

Aim: To observe the effects of a novel all-trans retinoid acid (ATRA) derivative, N-(3-trifluoromethyl-phenyl)-retinamide (ATPR), on lung adenocarcinoma A549 cells and to explore the potential mechanism of ATPR inhibiting of A549 cell migration. Materials and Methods: The cytotoxicity of ATRA and ATPR on A549 cells was assessed using MTT assay. Wound healing assays were used to analyze the influences of ATRA, ATPR, ML-7 (a highly selective inhibitor of myosin light chain kinase (MLCK)), PMA (an activator of MAPKs) and PD98059 (a selective inhibitor of ERK1/2) on the migration of A549 cells. Expression of MLCK and phosphorylation of myosin light chain (MLC) were assessed by Western blotting. Results: ATRA and ATPR inhibited the proliferation of A549 cells in a dose- and time-dependent manner, and the effect of ATPR was much more remarkable compared with ATRA. Relative migration rate and migration distance of A549 cells both decreased significantly after treatment with ATPR or ML-7. The effect on cell migration of PD98059 combining ATPR treatment was more notable than that of ATPR alone. Moreover, compared with control groups, the expression levels of MLCK and phosphorylated MLC in A549 cells were both clearly reduced in ATRA and ATPR groups. Conclusions: ATPR could suppress the migration and invasion of A549 cells, and the mechanism might be concerned with down-regulating the expression of MLCK in the ERK-MAPK signaling pathway, pointing to therapeutic prospects in lung cancer.