Zinc complex of 3,5-di-tert-butyl salicylate (Zn{[CH3)3C]2Sal}22-) is a zinc ion chelate of salicylate. In this study, we found that it inhibits the proliferation, invasion, migration and induce apoptosis of triple-negative breast cancer 4T1 cells. The results of RNA-seq showed that expression of 17 genes was up-regulated and 26 genes was down-regulated significantly by Zn{[CH3)3C]2Sal}22- treatment. Further GO analysis and KEGG analysis showed that the activity of Zn{[CH3)3C]2Sal}22- against

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... iple-negative breast cancer cells may be involved JAK-STAT3, HIF-1, and TNF signaling pathways. The expression of key genes was verified by RT-PCR. The phosphorylation of STAT3 and its upstream SRC decreased drastically upon Zn{[CH3)3C]2Sal}22- treatment as analyzed by western blot. Our results indicate that Zn{[CH3)3C]2Sal}22- inhibits the activity of TNBC cells by down-regulating STAT3 signaling pathway.