三阴性乳腺癌（TNBC）是一种极具侵袭性和快速进展的癌症，现有疗法对患者的效果很小。从紫草根中提取的β，β-二甲基丙烯酰茜素（DMAS）是一种具有强效抗癌活性的萘醌化合物。然而，DMAS对TNBC的抗肿瘤功能仍需证明。探究DMAS对TNBC的影响，并澄清其作用机制。运用网络药理学、转录组学及各种细胞功能实验，对TNBC细胞进行研究，以探究DMAS对TNBC的影响。并在异种移植动物模型中进行了进一步验证。MTT、EdU、Transwell、Scratch实验、流式细胞术、免疫荧光和免疫印迹等方法，评估了DMAS对三种TNBC细胞系的活性。通过在BT-549细胞中过表达和敲降STAT3，澄清了DMAS的抗TNBC机制。利用异种移植鼠模型分析了DMAS的体内效力。体外分析表明，DMAS抑制了G2/M期转换，抑制了TNBC增殖。此外，DMAS通过对抗上皮-间充质转化，触发线粒体依赖性凋亡，减少了细胞迁移。机理方面，DMAS通过抑制STAT3Y705磷酸化来发挥其抗肿瘤作用。STAT3过表达消除了DMAS的抑制作用。进一步的研究表明，DMAS治疗可以抑制TNBC在异种移植模型中的生长。值得注意的是，DMAS增强了TNBC对紫杉醇的敏感性，并通过下调免疫检查点PD-L1抑制了免疫逃逸。我们的研究首次揭示了DMAS通过抑制STAT3通路来增强紫杉醇的活性，抑制免疫逃逸和TNBC进展的潜力，有望成为TNBC的有前途的药物。版权所有©2023 Elsevier GmbH。保留所有权利。

Triple negative breast cancer (TNBC) is an extremely aggressive and rapidly progressing cancer, wherein existing therapies provide little benefit to patients. β, β-Dimethylacrylshikonin (DMAS), an active naphthoquinone derived from comfrey root, has potent anticancer activity. However, the antitumor function of DMAS against TNBC remains to be proved.Explore effects of DMAS on TNBC and clarify the mechanism.Network pharmacology, transcriptomics and various cell functional experiments were applied to TNBC cells to explore the effects of DMAS on TNBC. The conclusions were further validated in xenograft animal models.MTT, EdU, transwell, scratch tests, flow cytometry, immunofluorescence, and immunoblot were utilized to assess the activity of DMAS on three TNBC cell lines. The anti-TNBC mechanism of DMAS was clarified by overexpression and knockdown of STAT3 in BT-549 cells. In vivo efficacy of DMAS was analysed using a xenograft mouse model.In vitro analysis revealed that DMAS inhibited the G2/M phase transition and suppressed TNBC proliferation. Additionally, DMAS triggered mitochondrial-dependent apoptosis and reduced cell migration by antagonizing epithelial-mesenchymal transition. Mechanistically, DMAS exerted its antitumour effects by inhibiting STAT3Y705 phosphorylation. STAT3 overexpression abolished the inhibitory effect of DMAS. Further studies showed that treatment with DMAS inhibited TNBC growth in a xenograft model. Notably, DMAS potentiated the sensitivity of TNBC to paclitaxel and inhibited immune evasion by downregulating the immune checkpoint PD-L1.For the first time, our study revealed that DMAS potentiates paclitaxel activity, suppresses immune evasion and TNBC progression by inhibiting STAT3 pathway. It has the potential as a promising agent for TNBC.Copyright © 2023 Elsevier GmbH. All rights reserved.