• Korean Journal of Plant Resources
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• v.36 no.3
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• pp.207-218
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• 2023

Hepatocellular carcinoma (HCC) has a poor prognosis and high metastasis and recurrence rates. Although extracts of Alnus hirsuta (Turcz. ex Spach) Rupr. (AH) have been demonstrated to possess potential anti-inflammatory and anti-cancer activities, the underlying mechanism of AH in HCC treatment remains to be elucidated. We investigated the effects and potential mechanisms of AH on migration and invasion of Hep3B cells. Within the non-cytotoxic concentration range, AH significantly inhibited motility and invasiveness of Hep3B cells in a concentration-dependent manner. Inhibitory effects of AH on cell invasiveness are associated with tightening of tight junctions (TJs), as demonstrated by an increase in transepithelial electrical resistance. Immunoblotting indicated that AH decreased levels of claudins, which form major components of TJs and play key roles in the control and selectivity of paracellular transport. Furthermore, AH inhibited the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and simultaneously increased the levels of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. These effects were related to inactivation of the phosphoinositide 3-kinase (PI3K)/AKT pathway in Hep3B cells. Therefore, AH inhibits migration and invasion of Hep3B cells by inhibiting the activity of MMPs and tightening TJs through suppression of claudin expression, possibly by suppressing the PI3K/AKT signaling pathway.

• Molecules and Cells
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• v.37 no.10
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• pp.759-765
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• 2014

N-myc downstream-regulated gene 2 (NDRG2), which is known to have tumor suppressor functions, is frequently down-regulated in breast cancers and potentially involved in preventing the migration and invasion of malignant tumor cells. In the present study, we examined the inhibitory effects of NDRG2 overexpression, specifically focusing on the role of cyclooxygenase-2 (COX-2) in the migration of breast cancer cells. NDRG2 overexpression in MDA-MB-231 cells inhibited the expression of the COX-2 mRNA and protein, the transcriptional activity of COX-2, and prostaglandin $E_2$ ($PGE_2$) production, which were induced by a treatment with phorbol-12-myristate-13-acetate (PMA). Nuclear transcription factor-${\kappa}B$ (NF-${\kappa}B$) signaling attenuated by NDRG2 expression resulted in a decrease in PMA-induced COX-2 expression. Interestingly, the inhibition of COX-2 strongly suppressed PMA-stimulated migration and invasion in MDA-MB-231-NDRG2 cells. Moreover, siRNA-mediated knockdown of NDRG2 in MCF7 cells increased the COX-2 mRNA and protein expression levels and the PMA-induced COX-2 expression levels. Consistent with these results, the migration and invasion of MCF7 cells treated with NDRG2 siRNA were significantly enhanced following treatment with PMA. Taken together, our data show that the inhibition of NF-${\kappa}B$ signaling by NDRG2 expression is able to suppress cell migration and invasion through the down-regulation of COX-2 expression.

• Journal of Korean Biological Nursing Science
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• v.7 no.1
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• pp.47-56
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• 2005

nm23-H1 gene expression has been inversely correlated with tumor metastatic potential in certain tumors including melanomas, breast carcinomas, and hepatocellular carcinomas. However, its role with respect to the invasive behavior of central nervous system tumors has scarcely been addressed Because cell motility and invasion plays an essential role in metastatic dissemination, we have studied whether motile human glioma cell(U87MG) transfected with nm23-H1 complementary DNA have any alterations in their ability to migrate and invade. There was no significant changes in the shape and size of the cells following nm23-H1 transfection. The role of nm23-H1 in glioma migration and invasion have been evaluated by in vitro simple scratch technique and brain slice invasion model Basal migration ability of nm23-H1 transfectants cell(U87MG-pEGFP-nm23) were lesser than U87MG. Accordingly, U87MG-pEGFP-nm23 didn't migrate away apparently from the tumors implanted site comparing U87MG in brain slice invasion model. These results suggest that nm23-H1 may play an important role in suppressing the human glioma migration and invasion.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5403-5408
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• 2013

Objective: CXCL12 exerts a wide variety of chemotactic effects on cells. Evidence indicates that CXCL12, in conjunction with its receptor, CXCR4, promotes invasion and metastasis of tumor cells. Our objective was to explore whether the CXCL12-CXCR4 biological axis might influence biological behavior of pancreatic cancer cells. Methods: Miapaca-2 human pancreatic cancer cells were cultured under three different conditions: normal medium (control), medium + recombinant CXCL12 (CXCL12 group), or medium + CXCR4-inhibitor AMD3100 (AMD3100 group). RT-PCR was applied to detect mRNA expression levels of CXCL12, CXCR4, matrix metalloproteinase 2 (MMP-2), MMP-9, and human urokinase plasminogen activator (uPA). Additionally, cell proliferation and invasion were performed using CCK-8 colorimetry and transwell invasion assays, respectively. Results: CXCL12 was not expressed in Miapaca-2 cells, but CXCR4 was detected, indicating that these cells are capable of receiving signals from CXCL12. Expression of extracellular matrix-degrading enzymes MMP-2, MMP-9, and uPA was upregulated in cells exposed to exogenous CXCL12 (P<0.05). Additionally, both proliferation and invasion of pancreatic cancer cells were enhanced in the presence of exogenous CXCL12, but AMD3100 intervention effectively inhibited these processes (P<0.05). Conclusions: The CXCL12-CXCR4 biological axis plays an important role in promoting proliferation and invasion of pancreatic cancer cells.

• Korean Journal of Environmental Biology
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• v.40 no.4
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• pp.525-549
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• 2022

The process of biological invasion is led by the dynamics of a population as a demographic and evolutionary unit. Spatial structure can affect the population dynamics, and it is worth being considered in research on biological invasion which is always accompanied by dispersal. Metapopulation theory is a representative approach to spatially structured populations, which is chiefly applied in the field of ecology and evolutionary biology despite the controversy about its definition. In this study, metapopulation was considered as a spatially structured population that includes at least one subpopulation with significant extinction probability. The early phase of the invasion is suitable to be analyzed in aspects of the metapopulation concept because the introduced population usually has a high extinction probability, and their ecological·genetic traits determining the invasiveness can be affected by the metapopulation structure. Although it is important in the explanation of the prediction of the invasion probability, the metapopulation concept is rarely used in ecological research about biological invasion in Korea. It is expected that applying the metapopulation theory can supply a more detailed investigation of the invasion process at the population level, which is relatively inadequate in Korea. In this study, a framework dividing the invasive metapopulation into long- and middle-distance scales by the relative distance of movement to the natural dispersal range of species is proposed to easily analyze the effect of a metapopulation in real cases. Increased understanding of the mechanisms underlying invasions and improved prediction of future invasion risk are expected with the metapopulation concept and this framework.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.50-50
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• 2023

Prostaglandin E2(PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (Eps), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting Eps. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibititing the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinases (MMP)-9 as well as the down-regulation of COX-2 expression and PGE2 production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells. Through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8829-8836
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• 2014

Background: Cyclooxygenase-2 (COX-2), considered to have tumor-promoting potential, is highly expressed in a variety of tumors, including breast cancer. Since the functions and action mechanisms of COX-2 in breast cancer have not been fully elucidated, in the present study, the effects of target inhibiting COX-2 with recombinant adenovirus Ad-COX-2-shRNA on malignant biological behavior were investigated in representative cell lines. Materials and Methods: Breast cancer MDA-MB-231 and MCF-7 cells were transfected with Ad-COX-2-shRNA and COX-2 expression was tested by RT-PCR and Western blotting. Changes in proliferation, apoptosis and invasion of breast cancer cells were detected with various assays including MTT, colony forming, flowcytometry and Transwell invasion tests. The expression of related proteins involved in the cell cycle, apoptosis, invasion and signaling pathways was assessed by Western blotting. Results: COX-2 expression was significantly reduced in both breast cancer cell lines infected with Ad-COX-2-shRNA, with obvious inhibition of proliferation, colony forming rate, G2/M phase passage and invasion, as well as induction of apoptosis, in MDA-MB-231 and MCF-7 cells, respectively. At the same time, proteins related to the cell cycle, anti-apoptosis and invasion were significantly downregulated. In addition, c-myc expression and phosphorylation activation of Wnt/${\beta}$-catenin and p38MAPK pathways were reduced by the Ad-COX-2-shRNA. Conclusions: COX-2 expression is associated with proliferation, apoptosis and invasion of breast cancer cells, and its mechanisms of action involve regulating expression of c-myc through the p38MAPK and Wnt/${\beta}$-catenin pathways.

• Molecules and Cells
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• v.26 no.2
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• pp.107-112
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• 2008

Invasion mechanisms of pathogens and counteracting defense mechanisms of plants are highly diverse and perpetually evolving. While most classical studies of plant defense have focused only on defense-specific factor-mediated responses, recent work is beginning to shed light on the involvement of non-stress signal components, especially growth and developmental processes. This shift in focus links plant resistance more closely with growth and development. In this review, we summarize our current understanding of how pathogens manipulate host developmental processes and, conversely, of how plants deploy their developmental processes for self-protection. We conclude by introducing our recent work on UNI, a novel R protein in Arabidopsis which mediates cross-talk between developmental processes and defense responses.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.05a
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• pp.41-42
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• 2003

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.11-12
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• 2001