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2-Phenylnaphthyridin-4-one Derivative LYF-11 Inhibits Interleukin-6-mediated Epithelial-to-Mesenchymal Transition via the Inhibition of JAK2/STAT3 Signaling Pathway in MCF-7 Cells

Breast tumor interleukin-6 (IL-6) level increases with tumor grade, and elevated serum IL-6 correlates with poor survival in patients with breast cancer. Epithelial-mesenchymal transition (EMT) phenotypes are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Ther...

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Bibliographic Details
Published in:Anticancer research 2018-05, Vol.38 (5), p.2849-2859
Main Authors: Liu, Liang-Chih, Wu, Yao-Chung, Kuo, Sheng-Chu, Ho, Chi-Tang, Way, Tzong-DER, Chen, Shou-Tung
Format: Article
Language:English
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Summary:Breast tumor interleukin-6 (IL-6) level increases with tumor grade, and elevated serum IL-6 correlates with poor survival in patients with breast cancer. Epithelial-mesenchymal transition (EMT) phenotypes are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Therefore, we examined whether IL-6 induced EMT phenotype characterized in breast cancer cells. MCF-7 cells treated with different concentrations (10-50 ng/ml) of IL-6 for 24 and 48 h. Western blotting, flow cytometry, and cell migration assay were used to test whether IL-6 promoted tumor-initiating ability in MCF-7 cells. In this study, we found that the induction of EMT by IL-6 resulted in the acquisition of mesenchymal traits and the increase of tumor-initiating ability in MCF-7 cells. Moreover, we found that 2-phenylnaphthy-ridin-4-one derivatives were able to repress IL-6 induced EMT phenotype and tumor-initiating ability. Among these deriveratives, LYF-11 possessed the most potential inhibitory activity. LYF-11 effectively inhibited IL-6-induced EMT phenotype and tumor-initiating ability via the inhibition of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Our results suggest a connection between IL-6 receptor activity and EMT phenotype, and tumor-initiating ability. Moreover, LYF-11 is a potential compound for breast cancer therapy by targeting JAK2/STAT3 signaling pathway.
ISSN:0250-7005
1791-7530
DOI:10.21873/anticanres.12530