کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2124585 1547233 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Antiangiogenic effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Antiangiogenic effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor
چکیده انگلیسی

Angiogenesis is known to be required for tumour growth and metastasis. Recent reports indicated that phosphatidylinositol 3-kinase (PI3K) promoted angiogenesis by inducing expressions of HIF-1α and vascular endothelial growth factor (VEGF). The present study aims to investigate the antiangiogenic effect of ZSTK474, a novel pan-PI3K inhibitor. ZSTK474 significantly inhibited tumour growth in the RXF-631L xenograft model. Immunohistochemical staining of the tumour tissue with anti-von Willebrand Factor antibody showed a significantly reduced number of microvessels in the ZSTK474-treated mice, suggesting the highly promising antiangiogenic activity in vivo. In human umbilical vein endothelial cells (HUVECs), submicromolar concentrations of ZSTK474 inhibited cell growth, blocked VEGF-induced cell migration and the tube formation, and thus revealed potent in vitro antiangiogenic activity. Furthermore, ZSTK474 inhibited phosphorylation of Akt at submicromolar concentrations. In RXF-631L cancer cells, on the other hand, ZSTK474 treatment inhibited the expression of HIF-1α and secretion of VEGF. Together, these results suggest that ZSTK474 has potent antiangiogenic activity, which could be attributed to dual-target inhibitory properties: inhibition of VEGF secretion by cancer cells and inhibition of PI3K in endothelial cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Cancer - Volume 45, Issue 5, March 2009, Pages 857–865
نویسندگان
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