1. 泡参皂苷（PNS）是泡参的主要活性成分，可促进血管微循环。PNS在各种癌症中表现出抗肿瘤作用。然而，PNS与肿瘤血管之间关系的分子基础仍不清楚。 2. 为了研究PNS抑制乳腺癌生长和转移以及促进血管正常化之间的关系，我们在转基因小鼠模型MMTV-PyMT（FVB）自发性乳腺癌中进行了肿瘤微血管的激光散斑成像，观察了PNS对肿瘤生长和转移的影响。进行了肿瘤的Ki67和CD31的免疫组织化学染色，扫描电子显微镜用于观察肿瘤血管形态，流式细胞术用于检测肿瘤组织免疫微环境（TME）。 对小鼠肿瘤组织的主要血管进行了RNA-seq分析。在体外培养了HUVECs，以模拟肿瘤微环境并验证测序差异关键基因。 3. 经PNS处理后，我们观察到肿瘤生长受到了抑制，小鼠系统性肿瘤微血管的血流灌注增加，肺转移数量减少。此外，原发肿瘤的血管密度增加，血管外皮更加平滑和平整。此外，肿瘤微环境中的肿瘤相关巨噬细胞数量减少，肿瘤组织中的IL-6，IL-10和TNF-α表达水平也减少。 PNS下调了与肿瘤血管生成、迁移和黏附相关的多个基因的表达。在体外的管状结构实验中，我们发现PNS通过抑制EphA2的表达，促进了肿瘤血管的形成和连接，主要是规范化管道形态。此外，PNS在体内抑制了肿瘤血管标记蛋白和血管迁移粘附相关蛋白的表达。 4. 在这项研究中，我们发现PNS促进了肿瘤血管内皮细胞的生成和连接，揭示了EphA2在内皮细胞黏附和肿瘤血管形态中的关键作用。PNS可以通过抑制EphA2、改善乳腺癌的免疫微环境和促进肿瘤血管的正常化来抑制乳腺癌的增殖和转移。版权所有©2023 Elsevier GmbH发表。

Panax notoginseng saponins (PNS), the main active component of Panax notoginseng, can promote vascular microcirculation. PNS exhibits antitumor effects in various cancers. However, the molecular basis of the relationship between PNS and tumor blood vessels remains unclear.To study the relationship between PNS inhibiting the growth and metastasis of breast cancer and promoting the normalization of blood vessels.We performed laser speckle imaging of tumor microvessels and observed the effects of PNS on tumor growth and metastasis of MMTV-PyMT (FVB) spontaneous breast cancer in a transgenic mouse model. Immunohistochemical staining of Ki67 and CD31 was performed for tumors, scanning electron microscopy was used to observe tumor vascular morphology, and flow cytometry was used to detect tumor tissue immune microenvironment (TME). RNA-seq analysis was performed using the main vessels of the tumor tissues of the mice. HUVECs were cultured in tumor supernatant in vitro to simulate tumor microenvironment and verify the sequencing differential key genes.After treatment with PNS, we observed that tumor growth was suppressed, the blood perfusion of the systemic tumor microvessels in the mice increased, and the number of lung metastases decreased. Moreover, the vascular density of the primary tumor increased, and the vascular epidermis was smoother and flatter. Moreover, the number of tumor-associated macrophages in the tumor microenvironment was reduced, and the expression levels of IL-6, IL-10, and TNF-α were reduced in the tumor tissues. PNS downregulated the expression of multiple genes associated with tumor angiogenesis, migration, and adhesion. In vitro tubule formation experiments revealed that PNS promoted the formation and connection of tumor blood vessels and normalized the vessel morphology primarily by inhibiting EphA2 expression. In addition, PNS inhibited the expression of tumor vascular marker proteins and vascular migration adhesion-related proteins in vivo.In this study, we found that PNS promoted the generation and connection of tumor vascular endothelial cells, revealing the key role of EphA2 in endothelial cell adhesion and tumor blood vessel morphology. PNS can inhibit the proliferation and metastasis of breast cancer by inhibiting EphA2, improving the immune microenvironment of breast cancer and promoting the normalization of tumor blood vessels.Copyright © 2023. Published by Elsevier GmbH.