• 한국자원식물학회지
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• 제36권3호
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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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• 제37권10호
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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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• 제7권1호
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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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• 제14권9호
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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.

• 환경생물
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• 제40권4호
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• pp.525-549
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• 2022

개체군은 진화적 단위이자 개체군 통계적 단위로서, 생물학적 침입의 과정은 개체군의 생태적, 진화적 동태에 기인한다. 개체군의 공간구조는 개체군 동태에 영향을 줄 수 있으며, 분산이 반드시 동반되는 생물학적 침입에 대한 연구에서는 공간구조를 고려할 필요가 있다. 메타개체군 이론은 공간구조를 가진 개체군에 대한 대표적인 접근으로, 주로 생태학 및 진화생물학 연구에 활용되고 있다. 메타개체군은 공간적 구조를 가진 개체군의 동의어로 여겨지기도 하지만, 용어의 모호한 사용을 피하기 위해서는 절멸 가능성이 고려되는 경우에 한해 정의되어야 한다는 비판이 있다. 침입 초기 단계의 개체군은 높은 절멸 가능성을 가지는 경우가 많으므로, 메타개체군 이론을 적용하기에 용이하다. 한편, 침입 초기 개체군의 생태적·유전적 특성은 분산의 영향을 크게 받기 때문에, 메타개체군 이론은 개체군 수준에서 침입성의 변화와 침입 가능성을 설명하는 강력한 도구가 될 수 있을 것으로 생각된다. 그러나, 한국에서 침입생물에 대한 생태학적 연구는 주로 종 수준의 분포 변화에 대해 이루어지고 있고, 메타개체군 개념을 적용한 경우가 드문 실정이다. 메타개체군 이론을 활용한다면, 국내 연구가 상대적으로 미진했던 개체군 단위의 침입 기작을 보다 상세히 규명할 수 있을 것으로 생각된다. 본 연구에서는 실제 침입생물에 미치는 메타개체군의 영향을 쉽게 파악하기 위해 침입생물 메타개체군이 자연적인 분산 거리를 넘어서 연결되는지 여부에 따라 장거리와 중거리 두 가지 규모로 나누는 체계를 활용할 것을 제안하였다. 메타개체군 개념에 입각한 침입생물 연구가 침입의 기작을 이해하고 장래의 침입 리스크를 예측·관리하는 데에 도움을 줄 것으로 기대한다.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2023년도 임시총회 및 춘계학술대회
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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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• 제15권20호
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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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• 제26권2호
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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.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2003년도 춘계학술대회
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• pp.41-42
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• 2003

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2001년도 Korean Environmental Mutagen Society
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• pp.11-12
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• 2001