Aim
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. Materials and
Conclusion
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.
Methods
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.
Results
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.