지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
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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.
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참고문헌 (30)
참고문헌 신청
김형진 / 2005 / 방광암의 역학, 원인 및병인 / Korean J Uro-Oncol 3(1):1~11
Kirkali Z / 2005 / Bladder Cancer:Epidemiology, staging and grading, and diagnosis / Urology 66(6 suppl 1):4~34
정규원 / 2015 / Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2012 / Cancer Research and Treatment 47(2):127~141
Mueller J / 2013 / Management of muscle-invasive bladder cancer / Minerva Urol Nefrol 65(4):235~248
Peter Sidaway / 2016 / Bladder cancer: Atezolizumab effective against advanced-stage disease / Nature Reviews Urology 13(5):238~238
Kirkali Z / 2005 / Bladder Cancer:Epidemiology, staging and grading, and diagnosis / Urology 66(6 suppl 1):4~34
정규원 / 2015 / Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2012 / Cancer Research and Treatment 47(2):127~141
Mueller J / 2013 / Management of muscle-invasive bladder cancer / Minerva Urol Nefrol 65(4):235~248
Peter Sidaway / 2016 / Bladder cancer: Atezolizumab effective against advanced-stage disease / Nature Reviews Urology 13(5):238~238
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