最近治疗三阴性乳腺癌（TNBC）的治疗策略已将焦点从血管生长因子转移到内皮细胞代谢。这项研究强调了肿瘤周围电针的治疗潜力（一种全球公认的 TNBC 非药物干预措施）和分子机制的尚未开发的潜力。我们的研究表明，肿瘤周围电针有效降低了 4T1 乳腺癌异种移植物的微血管密度并增强了血管功能，在针灸后第 3 天效果最佳。瘤周电针的及时整合放大了紫杉醇的抗肿瘤功效。多组学分析揭示乙二醛酶 1 (Glo1) 和相关的甲基乙二醛糖酵解途径是电针诱导血管正常化的关键介质。瘤周电针显着降低 4T1 异种移植物内皮细胞中 Glo1 的表达。使用体内基质胶塞血管生成测定，我们证明了 Glo1 敲低或电针抑制血管生成。相反，Glo1 过度表达会增加血管形成。人脐静脉内皮细胞中 Glo1 的体外药理学抑制和基因敲除通过下调甲基乙二醛糖酵解途径抑制增殖并促进细胞凋亡。使用 Glo1 沉默斑马鱼模型的研究进一步支持了 Glo1 在血管发育中的作用。这项研究强调了 Glo1 在肿瘤周围电针中的关键作用，突出了增强血管正常化和改善 TNBC 治疗结果的有希望的途径。版权所有 © 2024。由 Elsevier B.V. 出版。

Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.Copyright © 2024. Published by Elsevier B.V.