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The Effect of Imiquimod on Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Malignant Melanoma Cell Invasion

 Jin Young Jung  ;  Hyun Sook Kim  ;  Mi Ryung Roh  ;  Hyo Jin Roh  ;  Sang Yoon Lee  ;  Kee Yang Chung 
 ANNALS OF DERMATOLOGY, Vol.26(3) : 363-373, 2014 
Journal Title
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Imiquimod ; Invasion ; Matrix metalloproteinase ; Melanoma ; Tissue inhibitor of metalloproteinase
Background: A number of reports have been published regarding the use of imiquimod for the treatment of melanoma in situ and metastatic melanoma. Essential steps in the process of melanoma invasion and metastasis include degradation of basement membranes and remodeling of the extracellular matrix by proteolytic enzymes, including matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Objective: To evaluate the antiinvasive effect of imiquimod in human malignant melanoma cell lines, SK-MEL-2 and SK-MEL-24, in vitro, and to investigate imiquimod-induced changes in the expression of MMPs and TIMPs. Methods: Invasiveness of melanoma cell lines following imiquimod treatment was evaluated by invasion assays. In order to investigate the mechanism of the anti-invasive effect of imiquimod, mRNA and protein levels of MMP-2, -9, membrane type 1 (MT1)-MMP, TIMP-1, and -2 were assessed by real-time reverse transcription-polymerase chain reaction, gelatin zymography, and western blotting. Results: Imiquimod treatment decreased in vitro viability of melanoma cells in a concentration-dependent manner. Imiquimod also elicited a concentration-dependent suppression of invasion in both melanoma cell lines. A concentration- dependent decrease in MMP-2 and MT1-MMP protein levels and a concentration-dependent increase in TIMP-1 and -2 protein levels by imiquimod was observed in both melanoma cell lines. However, expression of MMP-9 protein was increased in SK-MEL-2 but decreased in SK-MEL-24 with increasing imiquimod concentrations. Imiquimod elicited alterations in MMPs and TIMPs mRNA levels that parallel the observed changes in protein levels. Conclusion: Imiquimod may elicit an anti-invasive effect on human melanoma cells by regulating
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1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Roh, Mi Ryung(노미령) ORCID logo https://orcid.org/0000-0002-6285-2490
Roh, Hyo Jin(노효진)
Chung, Kee Yang(정기양) ORCID logo https://orcid.org/0000-0003-3257-0297
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