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Combretastatin A4 磷酸诱导血管内皮细胞程序性细胞死亡。

Combretastatin A4 phosphate induces programmed cell death in vascular endothelial cells.

机构信息

Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.

出版信息

Oncol Res. 2011;19(7):303-9. doi: 10.3727/096504011x13079697132790.

DOI:10.3727/096504011x13079697132790
PMID:21936400
Abstract

Combretastatin A4 phosphate (CA4P) is currently undergoing clinical trials as a tumor vascular-targeting agent. Here, we defined the antivascular effect and programmed cell death (PCD) induced by CA4P in vascular endothelial cells. CA4P induced time- and dose-dependent antiproliferative activities against human umbilical vein endothelial cells (HUVECs), and caused G2/M arrest accompanied with DNA fragmentation. The in vitro wound assay and tube formation assay indicated that CA4P potently inhibited migration of endothelial cells and tube formation. The apoptosis and autophagy marker microtubule-associated protein light chain 3 (LC3)-II was induced in CA4P-treated HUVECs. The current study demonstrates that CA4P is a promising antivascular agent with potent PCD-inducing activities. CA4P may be useful in the treatment of cancer and hemangioma.

摘要

Combretastatin A4 磷酸(CA4P)目前正在作为一种肿瘤血管靶向药物进行临床试验。在这里,我们定义了 CA4P 在血管内皮细胞中诱导的抗血管生成作用和程序性细胞死亡(PCD)。CA4P 诱导人脐静脉内皮细胞(HUVEC)的时间和剂量依赖性抗增殖活性,并导致 G2/M 期阻滞,伴有 DNA 片段化。体外划痕实验和管形成实验表明 CA4P 能有效抑制内皮细胞的迁移和管形成。CA4P 处理的 HUVEC 中诱导了凋亡和自噬标志物微管相关蛋白轻链 3(LC3)-II。本研究表明 CA4P 是一种有前途的抗血管生成药物,具有很强的 PCD 诱导活性。CA4P 可能对癌症和血管瘤的治疗有用。

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