Chen Heng, Wang Dong, Fan Limei, Liu Zixin, Zhang Weiran, Xu Jinhua, Liu Yunyi
School of Medicine, Jianghan University, Wuhan, 430056, Hubei, China.
Sci Rep. 2022 Mar 16;12(1):4545. doi: 10.1038/s41598-022-08704-0.
The zinc complex of 3,5-di-tert-butyl salicylate (Zn{[CH)C]Sal}) is a zinc ion chelate of salicylate. In this study, we found that this compound inhibits viability, invasion, and migration and induces apoptosis in triple-negative breast cancer 4T1 cells. RNA-seq showed that the expression of 17 genes was upregulated and 26 genes were downregulated significantly by Zn{[CH)C]Sal} treatment. Further GO and KEGG analysis showed that the activity of Zn{[CH)C]Sal} against triple-negative breast cancer cells may be involved in the 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{[CH)C]Sal} treatment, as demonstrated by western blot. Our results indicate that Zn{[CH)C]Sal} inhibits the activity of TNBC cells by downregulating the STAT3 signaling through the SRC pathway.
3,5-二叔丁基水杨酸锌配合物（Zn{[CH)C]Sal}）是水杨酸的锌离子螯合物。在本研究中，我们发现该化合物可抑制三阴性乳腺癌4T1细胞的活力、侵袭和迁移，并诱导其凋亡。RNA测序显示，经Zn{[CH)C]Sal}处理后，17个基因的表达上调，26个基因的表达显著下调。进一步的基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析表明，Zn{[CH)C]Sal}对三阴性乳腺癌细胞的作用可能涉及JAK-STAT3、HIF-1和TNF信号通路。通过逆转录聚合酶链反应（RT-PCR）验证了关键基因的表达。蛋白质免疫印迹法显示，经Zn{[CH)C]Sal}处理后，信号转导和转录激活因子3（STAT3）及其上游的Src的磷酸化显著降低。我们的结果表明，Zn{[CH)C]Sal}通过Src途径下调STAT3信号，从而抑制三阴性乳腺癌细胞的活性。
