Qi Yu, Xu Bo, He Jinrong, Jiang Bo, Yan Le, Zhou Haiyan, Chen Saili
Traditional Chinese Medicine Classics Laboratory, Hubei University of Chinese Medicine, Wuhan, People's Republic of China.
Postdoctoral Mobile Workstation, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China.
Drug Des Devel Ther. 2024 Dec 27;18:6263-6281. doi: 10.2147/DDDT.S492047. eCollection 2024.
Triple-negative breast cancer (TNBC) is a disease associated with high incidence and high mortality, which is a major problem threatening women's health. Xiaoyao Sanjie Decoction (XYSJD) exhibits remarkable therapeutic efficacy on TNBC; however, the underlying mechanism is unclear. This study verified the efficacy of XYSJD and its active component in the treatment of TNBC and explored its potential mechanism.
Ultra-high performance liquid chromatography-hybrid quadrupole orbitrap mass spectrometry (UHPLC-Q Exactive HFX-MS) was applied to explore the main chemical constituents of XYSJD. The key targets and potential mechanisms of XYSJD in the treatment of TNBC were predicted through network pharmacology, bioinformatics analysis and molecular docking. The effects of XYSJD against TNBC cells were evaluated by CCK-8 assay, EdU assay, wound healing assay, transwell assay, Hoechst-PI staining and flow cytometry. The mechanism of action was validated by Western blot analysis. Finally, the effect and mechanism of XYSJD and Que on TNBC were further verified by the tumor formation model.
UHPLC-Q Exactive HFX-MS identified a total of 9 compounds in XYSJD. Network pharmacological methods identified 206 targets for anti-TNBC. Bioinformatics analysis suggests that the EZH2/AKT1 signaling pathway might play an important role in the effects of XYSJD against TNBC. Gene Ontology enrichment analysis showed that the biological process of XYSJD in TNBC treatment mainly involved apoptosis. XYSJD and Que were observed to have a good anticancer effect in vivo and in vitro. In addition, quercetin could induce the apoptosis of TNBC cells by decreased the expression levels of EZH2/AKT1 signaling pathway. Furthermore, AKT1 overexpression, treatment with the AKT activator (SC79) and EZH2 overexpression could reverse apoptosis induced by quercetin in TNBC cells.
This study revealed the anti-TNBC efficacy of XYSJD. Quercetin, the effective component of XYSJD, promoted apoptosis of TNBC cells via blockade of the EZH2/AKT1 signaling pathway. These findings aim to provide a more reliable basis for the clinical application of XYSJD in the treatment of TNBC.
三阴性乳腺癌（TNBC）是一种发病率和死亡率均较高的疾病，是威胁女性健康的主要问题。逍遥散结汤（XYSJD）对TNBC具有显著的治疗效果；然而，其潜在机制尚不清楚。本研究验证了XYSJD及其活性成分在治疗TNBC中的疗效，并探讨其潜在机制。
采用超高效液相色谱-混合四极杆轨道阱质谱（UHPLC-Q Exactive HFX-MS）法探究XYSJD的主要化学成分。通过网络药理学、生物信息学分析和分子对接预测XYSJD治疗TNBC的关键靶点和潜在机制。采用CCK-8法、EdU法、伤口愈合实验、Transwell实验、Hoechst-PI染色和流式细胞术评估XYSJD对TNBC细胞的作用。通过蛋白质免疫印迹分析验证作用机制。最后，通过肿瘤形成模型进一步验证XYSJD和槲皮素对TNBC的作用及机制。
UHPLC-Q Exactive HFX-MS共鉴定出XYSJD中的9种化合物。网络药理学方法确定了206个抗TNBC靶点。生物信息学分析表明，EZH2/AKT1信号通路可能在XYSJD抗TNBC作用中发挥重要作用。基因本体富集分析表明，XYSJD在TNBC治疗中的生物学过程主要涉及细胞凋亡。观察到XYSJD和槲皮素在体内外均具有良好的抗癌作用。此外，槲皮素可通过降低EZH2/AKT1信号通路的表达水平诱导TNBC细胞凋亡。此外，AKT1过表达、用AKT激活剂（SC79）处理和EZH2过表达可逆转槲皮素诱导的TNBC细胞凋亡。
本研究揭示了XYSJD的抗TNBC疗效。XYSJD的有效成分槲皮素通过阻断EZH2/AKT1信号通路促进TNBC细胞凋亡。这些发现旨在为XYSJD在TNBC治疗中的临床应用提供更可靠的依据。
