那可丁调节缺氧诱导的血管生成和血液动力学:斑马鱼模型研究的启示

IF 3.5 4区 医学 Q2 CHEMISTRY, MEDICINAL Drug Development Research Pub Date : 2024-05-05 DOI:10.1002/ddr.22195
Jhansi Nathan, Rabiathul Shameera, Kaniha Sivakumar, Soundarya Rajendran, Elumalai Perumal
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引用次数: 0

摘要

我们利用骨肉瘤细胞株(MG-63)在体外和斑马鱼模型在体内研究了诺卡平的血管生成调节能力。我们对骨肉瘤细胞株(MG-63)进行了 MTT 试验和划痕伤口愈合试验,分别分析了那可汀的细胞毒性作用和抗移行能力。我们还通过分析受精后 24、48 和 72 小时斑马鱼胚胎的血管,即背主动脉和节间血管的发育情况,观察了诺卡平对斑马鱼胚胎的抗血管生成能力。利用实时聚合酶链反应分析了缺氧信号分子在 MG-63 细胞和斑马鱼胚胎中的基因表达。划痕伤口愈合的研究结果表明,在缺氧和常氧条件下,诺卡平都能阻止 MG-63 癌细胞迁移。在缺氧和常氧条件下,诺卡平都能显著降低斑马鱼胚胎的血管发育和心率,这表明了诺卡平对血液动力学的影响。诺卡平还能降低氯化钴(CoCl2)诱导的缺氧信号分子在 MG-63 细胞和斑马鱼胚胎中的基因表达。因此,无论在常氧还是缺氧条件下,诺卡平都能阻止 MG-63 癌细胞的增殖和迁移,并减少体内新血管的形成和与血管生成有关的生长因子的产生。
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Noscapine modulates hypoxia-induced angiogenesis and hemodynamics: Insights from a zebrafish model investigation

We investigated the angiogenesis-modulating ability of noscapine in vitro using osteosarcoma cell line (MG-63) and in vivo using a zebrafish model. MTT assay and the scratch wound healing assay were performed on the osteosarcoma cell line (MG-63) to analyze the cytotoxic effect and antimigrative ability of noscapine, respectively. We also observed the antiangiogenic ability of noscapine on zebrafish embryos by analyzing the blood vessels namely the dorsal aorta, and intersegmental vessels development at 24, 48, and 72 h postfertilization. Real-time polymerase chain reaction was used to analyze the hypoxia signaling molecules' gene expression in MG-63 cells and zebrafish embryos. The findings from the scratch wound healing demonstrated that noscapine stopped MG-63 cancer cells from migrating under both hypoxia and normoxia. Blood vessel development and the heart rate in zebrafish embryos were significantly reduced by noscapine under both hypoxia and normoxia which showed the hemodynamics impact of noscapine. Noscapine also downregulated the cobalt chloride (CoCl2) induced hypoxic signaling molecules' gene expression in MG-63 cells and zebrafish embryos. Therefore, noscapine may prevent MG-63 cancer cells from proliferating and migrating, as well as decrease the formation of new vessels and the production of growth factors linked to angiogenesis in vivo under both normoxic and hypoxic conditions.

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来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
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