罗硝唑通过 VEGF/Flk1 机制促进大鼠血管内皮细胞生长和 B16F10 细胞移植瘤血管生成。
VEGF/Flk1 Mechanism is Involved in Roxarsone Promotion of Rat Endothelial Cell Growth and B16F10 Xenograft Tumor Angiogenesis.
机构信息
College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China.
出版信息
Sci Rep. 2019 Nov 22;9(1):17417. doi: 10.1038/s41598-019-53870-3.
The potential angiogenic effect of roxarsone, a feed additive widely used to promote animal growth worldwide, was demonstrated recently. We explored the mechanism of vascular endothelial growth factor (VEGF) and its receptor (VEGFR) in roxarsone promotion of rat vascular endothelial cells (ECs) and B16F10 mouse xenografts. ECs were treated with 0.1-50 μM roxarsone or with roxarsone plus 10 ng/mL VEGF, VEGFR1 (Flt1), or VEGFR2 (Flk1) antibodies for 12-48 h to examine their role in cell growth promotion. Small interfering RNA (siRNA) targeting Vegf, Flt1, and Flk1 were transfected in the ECs, and we measured the expression level, cell proliferation, migration, and tube formation ability. The siRNA targeting Vegf or Flk1 were injected intratumorally in the B16F10 xenografts of mice that received 25 mg/kg roxarsone orally. Cell viability and VEGF expression following roxarsone treatment were significantly higher than that of the control (P < 0.05), peaking following treatment with 1.0 μM roxarsone. Compared to roxarsone alone, the VEGF antibody decreased cell promotion by roxarsone (P < 0.05), and the Flk1 antibody greatly reduced cell viability compared to the Flt1 antibody (P < 0.01). Roxarsone and Flk1 antibody co-treatment increased supernatant VEGF significantly, while cellular VEGF was obviously decreased (P < 0.01), whereas there was no significant difference following Flt1 antibody blockade. The siRNA against Vegf or Flk1 significantly attenuated the roxarsone promotion effects on EC proliferation, migration, and tube-like formation (P < 0.01), whereas the siRNA against Flt1 effected no obvious differences. Furthermore, the RNA interference significantly weakened the roxarsone-induced increase in xenograft weight and volume, and VEGF and Flk1 expression. Roxarsone promotion of rat EC growth, migration, and tube-like formation in vitro and of B16F10 mouse xenograft model tumor growth and angiogenesis involves a VEGF/Flk1 mechanism.
罗沙胂是一种被广泛用于促进全球动物生长的饲料添加剂，具有潜在的血管生成作用。最近，我们研究了罗沙胂促进大鼠血管内皮细胞（ECs）和 B16F10 小鼠异种移植物的血管内皮生长因子（VEGF）及其受体（VEGFR）的机制。将 0.1-50 μM 罗沙胂或罗沙胂加 10ng/ml VEGF、VEGFR1（Flt1）或 VEGFR2（Flk1）抗体处理 ECs 12-48 小时，以研究它们在细胞生长促进中的作用。用针对 Vegf、Flt1 和 Flk1 的小干扰 RNA（siRNA）转染 ECs，并测量其表达水平、细胞增殖、迁移和管状形成能力。将针对 Vegf 或 Flk1 的 siRNA 注射到接受 25mg/kg 罗沙胂口服的 B16F10 异种移植物的肿瘤内。与对照组相比，罗沙胂处理后的细胞活力和 VEGF 表达显著升高（P<0.05），在 1.0 μM 罗沙胂处理时达到峰值。与罗沙胂单独处理相比，VEGF 抗体降低了罗沙胂对细胞的促进作用（P<0.05），而 Flk1 抗体与 Flt1 抗体相比，大大降低了细胞活力（P<0.01）。罗沙胂和 Flk1 抗体共同处理显著增加了上清液 VEGF，而细胞内 VEGF 明显减少（P<0.01），而 Flt1 抗体阻断后则没有明显差异。针对 Vegf 或 Flk1 的 siRNA 显著减弱了罗沙胂对 EC 增殖、迁移和管状形成的促进作用（P<0.01），而针对 Flt1 的 siRNA 则没有明显差异。此外，RNA 干扰显著减弱了罗沙胂诱导的异种移植物重量和体积增加以及 VEGF 和 Flk1 表达。罗沙胂促进大鼠 EC 的生长、迁移和管状形成以及 B16F10 小鼠异种移植物模型肿瘤生长和血管生成涉及 VEGF/Flk1 机制。
Zotero 插件