■抑制血管进入肿瘤基质以及动态细胞生长是关注的中心。这里,我们旨在研究vandetanib对乳腺癌干细胞(CSC)血管生成能力的影响。
■MDA-MB-231细胞暴露于不同剂量的vandetanib并监测存活率。血管内皮生长因子(VEGF)的刺激作用,成纤维细胞生长因子(FGF),在vandetanib处理的MDA-MB-231细胞中评估和表皮生长因子(EGF)。在Matrigel表面研究了体外小管发生能力。还在PI3K和/或Wnt3a抑制后评估了vandetanib对细胞存活的协同作用。血管内皮(VE)-钙黏着蛋白,基质金属蛋白酶-2(MMP-2),-9,Wnt3a,和p-Akt/Akt比率使用蛋白质印迹法测量。
■Vandetanib以剂量依赖性方式降低生存率(P<0.05)。与VEGF相关的增殖效应,FGF,在预先暴露于vandetanib的这些细胞中,EGF钝化(P<0.05)。1,5µM的vandetanib抑制了微循环模式的三阴性乳腺癌(TNBC)(P<0.05)。因此,1,5µM的vandetanib可能会降低CD24细胞的数量。1和5μM的vandetanib通过阻断PI3K和Wnt3a途径抑制细胞增殖,并降低p-Akt/Akt比率,Wnta3蛋白水平(P<0.05)。1和5µMvandetanib联合PI3K抑制剂可减少转移标志物,包括,MMP-2和MMP-9。同时治疗(PI3K,抑制剂+1,5µMvandetanib)也大大降低了上皮-间质转化(EMT)标志物,如VE-钙黏着蛋白(P<0.05)。
■Vandetanib通过钝化干细胞特性抑制了血管生成拟态(VM)网络,与CSCs中VE-cadherin的抑制相吻合。
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: Vandetanib suppressed vasculogenic mimicry (VM) networking through blunting stemness properties, coincided with suppression of VE-cadherin in CSCs.