國家衛生研究院 NHRI:Item 3990099045/8748
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    題名: Docosahexaenoic acid downregulates EGF-induced urokinase plasminogen zctivator and matrix metalloproteinase 9 expression by inactivating EGFR/ErbB2 signaling in SK-BR3 breast cancer cells
    作者: Li, CC;Yao, HT;Cheng, FJ;Hsieh, YH;Lu, CY;Wu, CC;Liu, KL;Chang, JW
    貢獻者: Institute of Molecular and Genomic Medicine
    摘要: Urokinase plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9) play crucial roles in tumor metastasis. Despite the well-known anticancer role of docosa-hexaenoic acid (DHA), its specific effect on ErbB2-mediated breast cancer metastasis is not fully clarified. In this study, we investigated the effect of DHA on epidermal growth factor (EGF)-induced uPA and MMP-9 activity, expression and cell invasion in SK-BR3 breast cancer cells and the possible mechanisms involved. The results showed that EGF (40 ng/ml) induced uPA and MMP-9 mRNA and protein expression, enzyme activity, and 100 μM DHA significantly inhibited EGF-induced uPA and MMP-9 mRNA, protein expression, enzyme activity, cell migration, and cell invasion. EGF increased protein expression and phosphorylation of EGF receptor (EGFR) and ErbB2 as well as of JNK2, ERK1/2, and Akt, and these changes were attenuated by DHA pretreatment. AG1478, an inhibitor of EGFR, also attenuated EGF-induced activation of EGFR, JNK2, ERK1/2, and Akt. Knocked down ErbB2 expression resulted in a similar inhibition of uPA and MMP-9 expression as noted by DHA and AG1478. Taken together, these results suggest that suppression of EGF-induced metastasis by DHA is likely through an inhibition of EGFR and ErbB2 protein expression and the downstream target uPA and MMP-9 activation in SK-BR3 human breast cancer cells.
    日期: 2015-07
    關聯: Nutrition and Cancer. 2015 Jul;67(5):771-782.
    Link to: http://dx.doi.org/10.1080/01635581.2015.1037961
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0163-5581&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000357020600007
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84934436274
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