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青蒿琥酯抑制小鼠血管内皮瘤细胞的增殖和侵袭以及肿瘤生长。

Artesunate inhibits proliferation and invasion of mouse hemangioendothelioma cells and of tumor growth .

作者信息

Wang Ning, Chen Hongxia, Teng Yinping, Ding Xionghui, Wu Huan, Jin Xianqing

机构信息

Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Medical University, Yuzhong, Chongqing 400014, P.R. China.

Key Laboratory of Pediatrics in Chongqing, Chongqing Medical University, Yuzhong, Chongqing 400014, P.R. China.

出版信息

Oncol Lett. 2017 Nov;14(5):6170-6176. doi: 10.3892/ol.2017.6986. Epub 2017 Sep 18.

Abstract

Artesunate has been demonstrated to be a novel potential antitumor agent in numerous studies. However, its efficacy in infantile hemangioma is unknown. The aim of the present study was to investigate the role of artesunate in the control of vascular tumor biological behavior and molecular mechanism using mouse hemangioendothelioma endothelial (EOMA) cells and a nude mouse model. Cell viability, apoptosis and invasion were determined by an MTT assay, flow cytometric analysis and Transwell invasion assay, respectively. Reverse transcription-quantitative polymerase chain reaction and western blotting were utilized to examine the expression of genes and proteins. Inoculated EOMA cells were injected into the subcutaneous tissues of nude mice to observe the effect of artesunate therapy on the vascular tumor, an effect that was similar to that of pingyangmycin (PYM). It was identified that artesunate treatment (0-600 µg/ml) inhibited cell growth in a time- and dose-dependent manner. Artesunate at 300 µg/ml significantly reduced the proliferation and invasion of EOMA cells, and significantly decreased the expression of vascular endothelial growth factor (VEGF)-A, VEGFR-1, VEGFR-2 and hypoxia inducible factor-1α over time; caspase-3 was simultaneously upregulated . Artesunate significantly inhibited tumor growth, and the curative effect was similar to that observed with PYM . It was concluded that artesunate could effectively inhibit the growth of vascular tumors, and thus could be a novel drug candidate for the treatment of infantile hemangioma.

摘要

在众多研究中,青蒿琥酯已被证明是一种新型潜在抗肿瘤药物。然而,其在婴儿血管瘤中的疗效尚不清楚。本研究的目的是利用小鼠血管内皮瘤内皮(EOMA)细胞和裸鼠模型,研究青蒿琥酯在控制血管肿瘤生物学行为和分子机制中的作用。分别通过MTT法、流式细胞术分析和Transwell侵袭试验测定细胞活力、凋亡和侵袭。利用逆转录定量聚合酶链反应和蛋白质印迹法检测基因和蛋白质的表达。将接种的EOMA细胞注射到裸鼠皮下组织中,观察青蒿琥酯治疗对血管肿瘤的影响,其效果与平阳霉素(PYM)相似。结果表明,青蒿琥酯处理(0 - 600μg/ml)以时间和剂量依赖性方式抑制细胞生长。300μg/ml的青蒿琥酯随着时间的推移显著降低了EOMA细胞的增殖和侵袭,并显著降低了血管内皮生长因子(VEGF)-A、VEGFR-1、VEGFR-2和缺氧诱导因子-1α的表达;同时caspase-3上调。青蒿琥酯显著抑制肿瘤生长,其疗效与PYM相似。结论是,青蒿琥酯可有效抑制血管肿瘤的生长,因此可能是治疗婴儿血管瘤的一种新型候选药物。

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