• BMB Reports
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• 제47권12호
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• pp.691-696
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• 2014

${\alpha}$-Enolase is a glycolytic enzyme and a surface receptor for plasminogen. ${\alpha}$-Enolase-bound plasminogen promotes tumor cell invasion and cancer metastasis by activating plasmin and consequently degrading the extracellular matrix degradation. Therefore, ${\alpha}$-enolase and plasminogen are novel targets for cancer therapy. We found that the amino acid sequence of a peptide purified from enzymatic hydrolysates of seahorse has striking similarities to that of ${\alpha}$-enolase. In this study, we report that this peptide competes with cellular ${\alpha}$-enolase for plasminogen binding and suppresses urokinase plasminogen activator (uPA)-mediated activation of plasminogen, which results in decreased invasive migration of HT1080 fibrosarcoma cells. In addition, the peptide treatment decreased the expression levels of uPA compared to that of untreated controls. These results provide new insight into the mechanism by which the seahorse-derived peptide suppresses invasive properties of human cancer cells. Our findings suggest that this peptide could emerge as a potential therapeutic agent for cancer.

• 생명과학회지
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• 제22권7호
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• pp.964-969
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• 2012

Genistein은 대두 및 그들의 부산물에 풍부하게 존재하는 isoflavone의 일종으로 정상세포에서는 독성을 나타내지 않는 범위에서 다양한 in vitro 및 in vivo 모델에서 암세포의 증식을 효과적으로 억제할 수 있는 천연물로 알려져 있다. 본 연구에서는 MCF-7 및MDA-MB-231 유방암세포에서 matrix metalloproteinases (MMPs)의 활성 및 발현과 침윤성에 미치는 genistein의 영향을 조사하였다. 본 연구의 결과에 의하면 genistein은 12-O-tetradecanoyl phorbol-13-acetate (TPA) 처리에 의하여 활성화된 MMP-2 및 -9의 활성을 유의적으로 차단하였으며, 이는 전사 및 번역 수준에서 MMP-2 및 -9의 발현 억제와 연관성이 있었다. 또한 matrigel invasion assay를 통하여 genistein은 두 유방암세포의 침윤성을 완벽하게 차단하였음을 관찰하였으며, 이러한 효과는 genistein의 세포독성 효과에 의한 것이 아니었음을 알 수 있었다. 비록 in vivo 동물 실험을 통한 부가적인 연구의 필요성이 있으나, 본 연구의 결과는 genistein이 암의 전이를 억제할 수 있는 효과적인 식이 소재임을 보여주는 것이다.

• 대한한방내과학회지
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• 제37권1호
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• pp.65-76
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• 2016

Objectives: The purpose of this study was to identify the inhibitory effects of Hwangheuk-san (HHS), a Korean multi-herb formula comprising four medicinal herbs, on cell migration and invasion, two critical cellular processes that are often deregulated during metastasis, using the human bladder cancer 5637 cell line.Methods: Cell viability, motility, and invasion were assessed by 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphnyl-2H-tetrazolium bromide (MTT), wound healing migration, and Transwell assays, respectively. Gene expression was detected by Western blot analysis. In addition, the activities of matrix metalloproteinases (MMPs) and the values for transepithelial electrical resistance (TER) were analyzed using a Gelatinase Activity Assay Kit and an Epithelial Tissue Voltohmmeter, respectively.Results: Our data indicated that within the concentration range that was not cytotoxic, HHS effectively inhibited the cell motility and invasiveness of 5637 cells. HHS markedly decreased the expression and activity of MMP-2 and MMP-9, which was associated with unregulation of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2. Further investigation revealed that phosphorylation of phosphatidylinositol 3-kinase (PI3K) and AKT was decreased in HHS-treated 5637 cells, and a PI3K/AKT inhibitor synergistically reduced the inhibition of migration and invasion and also inactivated MMP-2 and MMP-9. Moreover, HHS increased the tightening of tight junctions (TJs), which was demonstrated by an increase in the TER, and reduced the expression the levels of claudin family members (claudin-3 and -4), which are major components involved in the tightening of TJs.Conclusions: The present findings demonstrated that HHS attenuated the migration and invasion of bladder cancer 5637 cells by modulating the activity of the PI3K/Akt signaling pathway and also through TJ tightening.

• 한국식품저장유통학회지
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• 제22권1호
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• pp.19-26
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• 2015

본 연구는 3,3'-diindolylmethane(DIM)이 인간전립선암 세포인 PC3 세포와 DU145 세포의 부착, 이동, 침윤에 미치는 영향을 살펴보았다. DIM은 PC3와 DU145 세포의 부착을 농도 의존적으로 억제하였다. 24시간동안 DIM으로 PC3 세포를 전 처리한 후 부착실험을 한 결과 농도 의존적으로 억제하였다. 그러나 암세포가 부착 시 DIM의 암세포 부착 억제가 전처리에 의한 부착 억제보다 효과적이었다. DIM은 인간 전립선암세포의 이동과 침윤도 억제하였으며 24시간 동안 PC3 세포를 DIM으로 전처리를 했을 때도 침윤 억제효과를 나타내었다. 또한 DIM의 억제효과는 세포주에 따라 다소 다른 경향을 보여 PC3 세포에 대한 억제효과가 DU145 세포에 대한 억제효과보다 큰 것으로 관찰되었다. DIM은 $150{\mu}M$ 까지 세포 독성이 관찰되지 않은 것으로 보고되고 있으므로 본 연구결과 DIM은 세포 독성이 없는 수준에서 인간 전립선암 세포인 PC3와 DU145 세포의 부착, 이동, 침윤을 효과적으로 억제하여 전립선암 전이 억제제로 이용될 수 있을 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2401-2406
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• 2013

From January 1, 2008 to March 31, 2010, 101 patients with stage II-III breast cancer were enrolled in this study and subjected to an anthracycline-based neoadjuvant chemotherapy regimen with or without docetaxel. Surgery was performed after 2-6 cycles of chemotherapy, and the clinical response was determined by pathological and histochemical assessments. The clinical response rate, as indicated by complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), were 6.9, 52.5, 36.6, and 4.0%, respectively. A multivariable correlation analysis indicated that the overall clinical response rate correlated with the number of metastatic lymph nodes, number of chemotherapy cycles, and vessel invasion status. Importantly, the CR rate was only associated with the number of chemotherapy cycles. Nonparametric tests failed to detect a correlation between HER2 or Topo $II{\alpha}$ status and clinical response to neoadjuvant chemotherapy in these patients. When they were stratified by HER2 or HR status, for HER2-positive patients the CR rate was associated with vessel invasion and Topo $II{\alpha}$ status. Based on our findings, we propose that HR, HER-2 and Topo $II{\alpha}$ are not putative predictive biomarkers of chemotherapy outcome for breast cancer patients. Topo $II{\alpha}$ expression level was only inversely correlated with CR rate among HR-positive patients. Importantly, the achievement of CR was largely related to the number of chemotherapy cycles.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1343-1348
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• 2015

Human UHRF1 (ubiquitin-like PHD and RING finger domain-containing 1) has been reported to be over-expressed in many cancers, but its role in ovarian cancer remains elusive. Here, we determined whether knockdown of UHRF1 by lentivirus-mediated shRNA could inhibit ovarian cancer cell growth. Lentivirus-mediated short hairpin RNAs (lv-shRNAs-UHRF1) were designed to trigger the gene silencing RNA interference (RNAi) pathway. The efficiency of lentivirus-mediated shRNA infection into HO-8910 and HO-8910 PM cells was determined using fluorescence microscopy to observe lentivirus-mediated GFP expression and was confirmed to be over 80 percent. UHRF1 expression in infected HO-8910 and HO-8910 PM was evaluated by real-time PCR and Western blot analysis. The Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability; flow cytometry and Hoechst 33342 assay was applied to measure cell cycle arrest and apoptosis. Cell invasion was assessed using transwell chambers. Our results demonstrated that the loss of UHRF1 promoted HO-8910 and HO-8910 PM cell apoptosis, while inhibiting cell proliferation. In addition, UHRF1 knockdown significantly inhibited the invasion of human ovarian cancer cells. In the present study, we also showed that depleting HO-8910 cells of UHRF1 caused activation of the DNA damage response pathway, with the cell cycle arrested in G2/M-phase. The DNA damage response in cells depleted of UHRF1 was illustrated by phosphorylation of CHK (checkpoint kinase) 2 on Thr68, phosphorylation of CDC25 (cell division control 25) on Ser 216 and phosphorylation of CDK1 (cyclin-dependent kinase 1) on Tyr 15.

• Molecules and Cells
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• 제37권9호
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• pp.664-671
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• 2014

MiR-217 can function as an oncogene or a tumour suppressor gene depending on cell type. However, the function of miR-217 in lung cancer remains unclear to date. This study aims to evaluate the function of miR-217 in lung cancer and investigate its effect on the sensitivity of lung cancer cells to cisplatin. The expression of miR-217 was detected in 100 patients by real-time PCR. The effects of miR-217 overexpression on the proliferation, apoptosis, migration and invasion of SPC-A-1 and A549 cells were investigated. The target gene of miR-217 was predicted by Targetscan online software, screened by dual luciferase reporter gene assay and demonstrated by Western blot. Finally, the effects of miR-217 up-regulation on the sensitivity of A549 cells to cisplatin were determined. The expression of miR-217 was significantly lower in lung cancer tissues than in noncancerous tissues (p < 0.001). The overexpression of miR-217 significantly inhibited the proliferation, migration and invasion as well as promoted the apoptosis of lung cancer cells by targeting KRAS. The up-regulation of miR-217 enhanced the sensitivity of SPC-A-1 and A549 cells to cisplatin. In conclusion, miR-217 suppresses tumour development in lung cancer by targeting KRAS and enhances cell sensitivity to cisplatin. Our results encourage researchers to use cisplatin in combination with miR-217 to treat lung cancer. This regime might lead to low-dose cisplatin application and cisplatin side-effect reduction.

• The Korean Journal of Pain
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• 제36권1호
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• pp.60-71
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• 2023

Background: The purpose of this research was to assess the role of heparanase (HPSE)/syndecan1 (SDC1)/nerve growth factor (NGF) on cancer pain from melanoma. Methods: The influence of HPSE on the biological function of melanoma cells and cancer pain in a mouse model was evaluated. Immunohistochemical staining was used to analyze HPSE and SDC1. HPSE, NGF, and SDC1 were detected using western blot. Inflammatory factors were detected using ELISA assay. Results: HPSE promoted melanoma cell viability, proliferation, migration, invasion, and tumor growth, as well as cancer pain, while SST0001 treatment reversed the promoting effect of HPSE. HPSE up-regulated NGF, and NGF feedback promoted HPSE. High expression of NGF reversed the inhibitory effect of HPSE down-regulation on melanoma cell phenotype deterioration, including cell viability, proliferation, migration, and invasion. SST0001 down-regulated SDC1 expression. SDC1 reversed the inhibitory effect of SST0001 on cancer pain. Conclusions: The results showed that HPSE promoted melanoma development and cancer pain by interacting with NGF/SDC1. It provides new insights to better understand the role of HPSE in melanoma and also provides a new direction for cancer pain treatment.

• International Journal of Stem Cells
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• 제15권4호
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• pp.415-421
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• 2022

Cancer initiation and progression are profoundly along with the crosstalk between cancer cells and the surrounding stroma. Accumulating evidence has shown that the therapy targeting the extracellular matrix (ECM) would regress tumor growth and invasion in the most common carcinomas. However, it remains largely unexplored in several rare tumors like odontogenic tumors. Ameloblastoma (AM) is the representative odontogenic epithelial tumor in the jawbone, and it usually infiltrates into adjacent bone marrow and has unlimited growth capacity and a high potential for recurrence. This study aims to investigate the role of collagen-rich ECM during the invasion of AM. Transcriptomic analysis revealed that ECM- and epithelial-to-mesenchymal transition (EMT)-related genes were up-regulated in AM compared to ameloblastoma cell line, AM-1. Tumoroid forming analysis showed that Collagen-rich ECM is indispensable for AM progression, especially for aggressive growth patterns and collective invasion.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.201-208
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• 2013

Objective: To investigate changes in the invasive capacity of gastric cancer cells in vitro after expression inhibition of T lymphoma invasion and metastasis inducing factor 1 (Tiam 1) and underlying mechanisms. Methods: Using adhesion selection, two subpopulations with high ($M_H$) or low ($M_L$) invasive capacity were separated from the human gastric cancer cell line MKN-45 ($M_0$). Tiam 1 antisense oligodeoxynucleotide (ASODN) was transfected into $M_H$ cells with liposomes, and expression of Tiam 1 mRNA and protein was determined by RT-PCR and quantitative cellular-ELISA. Changes in the cytoskeleton, invasive capacity in vitro and expression of ras-related $C_3$ botulinum toxin substrate 1 (Rac 1), integrin ${\beta}1$ and matrix metalloproteinase 2 (MMP 2) between Tiam 1 ASODN transfected $M_H$ cells and non-transfected cells were observed by HE staining, cytoskeletal protein staining, scanning electron microscopy, Boyden chamber tests and cyto-immunohistochemistry. Results: A positive correlation existed between the expression level of Tiam l mRNA or protein and the invasion capacity of gastric cancer cells. After ASODN treatment ($0.43{\mu}M$ for 48 h), Tiam 1 mRNA transcription and protein expression in $M_H$ cells were decreased by 80% and 24% respectively (P < 0.05), compared with untreated controls, while invasive capacity in vitro was suppressed by 60% (P < 0.05). Morphologic and ultrastructural observation also showed that ASODN-treated $M_H$ cells exhibited smooth surfaces with obviously reduced filopodia and microspikes, which resembled $M_0$ and $M_L$ cells. Additionally, cytoskeletal distribution dramatically altered from disorder to regularity with reduced long filament-like structure, projections, pseudopodia on cell surface, and with decreased acitn-bodies in cytoplasm. After Tiam 1 ASODN treatment, the expression of Rac 1 and Integrin ${\beta}1$ in $M_H$ cells was not affected (P > 0.05), but that of MMP 2 in $M_H$ cells was significantly inhibited compared with untreated cells (P < 0.05). Conclusion: Over-expression of Tiam-1 contributes to the invasive phenotype of gastric cancer cells. Inhibition of Tiam 1 expression could impair the invasive capacity of gastric cancer cells through modulating reconstruction of the cytoskeleton and regulating expression of MMP 2.