Recent studies have shown that stress can substantially facilitate breast cancer metastasis, which can be ameliorated by nonselective β1/β2-adrenergic receptor (β1/β2-AR) blocker. However, several side effects were identified. Thus, it is extremely warranted to explore more effective and better-tolerated β2-AR blocker. Currently, we demonstrated that baicalin (BA), a major bioactive component of Scutellaria baicalensis Georgi, could significantly attenuate stress hormones especially epinephrine (Epi)-induced breast cancer cell migration and invasion in vitro. Mechanistically, we identified that β2-AR was a direct target of BA via the drug affinity responsive target stability (DARTS) combined with mass spectrum assay, and BA photoaffinity probe with pull-down assay, which was further confirmed by a couple of biophysical and biochemical assays. Furthermore, we demonstrated that BA could directly bind to the Phe-193 and Phe-289 of β2-AR, subsequently inhibit cAMP-PKA-FAK pathway, and thus impede epithelial-mesenchymal transition (EMT), thereby hindering the metastatic progression of the chronic stress coupled with syngeneic and xenograft in vivo orthotopic and tail vein mouse model. These findings firstly identify BA as a potential β2-AR inhibitor in the treatment of stress-induced breast cancer metastasis.

最近的研究表明，压力可以极大地促进乳腺癌转移，可以通过非选择性 β1/β2-肾上腺素能受体 (β1/β2-AR) 阻滞剂来改善这种情况。然而，发现了一些副作用。因此，探索更有效、耐受性更好的β2-AR阻滞剂非常有必要。目前，我们证明黄芩苷（BA）是黄芩的主要生物活性成分，可在体外显着减弱应激激素尤其是肾上腺素（Epi）诱导的乳腺癌细胞迁移和侵袭。从机制上讲，我们通过药物亲和响应靶稳定性（DARTS）结合质谱测定以及BA光亲和探针结合pull-down测定确定β2-AR是BA的直接靶点，并通过一些生物物理和化学实验进一步证实。生化测定。此外，我们证明BA可以直接与β2-AR的Phe-193和Phe-289结合，随后抑制cAMP-PKA-FAK通路，从而阻碍上皮-间质转化（EMT），从而阻碍肿瘤的转移进展。慢性应激与同基因和异种移植体内原位和尾静脉小鼠模型相结合。这些发现首先确定 BA 是治疗应激诱导的乳腺癌转移的潜在 β2-AR 抑制剂。