对肿瘤基质中的血管生成抑制以及动态细胞生长的抑制成为关注的中心。本研究旨在检查万达替尼对乳腺癌干细胞（CSCs）血管生成能力的作用。将MDA-MB-231细胞暴露在不同剂量的万达替尼中，并监测其存活率。评估万达替尼处理的MDA-MB-231细胞中血管内皮生长因子（VEGF）、成纤维细胞生长因子（FGF）和表皮生长因子（EGF）的刺激效应。在Matrigel表面上研究体外血管形成能力。在PI3K和/或Wnt3a抑制后，还评估了万达替尼对细胞存活的协同效应。利用Western blotting测定血管内皮（VE）钙粘蛋白，基质金属蛋白酶-2（MMP-2）、-9，Wnt3a和p-Akt/Akt比值。万达替尼具有剂量依赖性地降低细胞存活率（P<0.05）。预先暴露于万达替尼的细胞中，与VEGF、FGF和EGF相关的增殖效应被抑制（P<0.05）。1, 5 µM万达替尼抑制了微循环模式的三阴性乳腺癌（TNBC）（P<0.05）。因此，1, 5 µM万达替尼有潜在的降低CD24-细胞的作用。1和5 µM万达替尼通过阻断PI3K和Wnt3a通路，降低p-Akt/Akt比值和Wnt3a蛋白水平（P<0.05），抑制了细胞增殖。与PI3K抑制剂结合应用的1和5 µM万达替尼减少了转移标志物，包括MMP-2和MMP-9。联合治疗（PI3K抑制剂+1、5 µM万达替尼）还显著降低了上皮-间充质转化（EMT）标志物，如VE钙粘蛋白（P<0.05）。万达替尼通过抑制干细胞特性和VE钙粘蛋白的抑制，抑制了血管样模拟（VM）网络的形成。© 2023作者。

The inhibition of vascularization into tumor stroma as well as dynamic cell growth is the center of attention. Here, we aimed to examine the role of vandetanib on angiogenesis capacity of breast cancer stem cell (CSCs).MDA-MB-231 cells were exposed to different doses of vandetanib and survival rate was monitored. Stimulatory effects of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) were evaluated in vandetanib-treated MDA-MB-231 cells. In vitro tubulogenesis capacity was studied on the Matrigel surface. The synergistic effects of vandetanib on cell survival were also assessed after PI3K and/or Wnt3a inhibition. Vascular endothelial (VE)-cadherin, matrix metalloproteinase-2 (MMP-2), -9, Wnt3a, and p-Akt/Akt ratio were measured using western blotting.Vandetanib reduced survival rate in a dose-dependent manner (P<0.05). Proliferative effects associated with VEGF, FGF, and EGF were blunted in these cells pre-exposed to vandetanib (P<0.05). The microcirculation pattern's triple-negative breast cancer (TNBC) was suppressed by 1, 5 µM of vandetanib (P<0.05). Hence 1, 5 µM of vandetanib potentially decreased the population of CD24- cells. 1 and 5 µM of vandetanib inhibited cell proliferation by blocking PI3K and Wnt3a pathways and decreased the p-Akt/Akt ratio, Wnta3 protein levels (P<0.05). 1 and 5 µM vandetanib combined with PI3K inhibitor diminished metastatic markers including, MMP-2, and MMP-9. The concurrent treatment (PI3K, inhibitor+ 1, 5 µM vandetanib) also considerably reduced epithelial-mesenchymal transition (EMT) markers such as VE-cadherin (P<0.05).Vandetanib suppressed vasculogenic mimicry (VM) networking through blunting stemness properties, coincided with suppression of VE-cadherin in CSCs.© 2023 The Author(s).