Inhibition of fatty acid synthase suppresses neovascularization via regulating the expression of VEGF-A in glioma

被引：29

作者：

Zhou, Yiqiang ^{[1
]}

Jin, Guishan ^{[1
]}

Mi, Ruifang ^{[1
]}

Zhang, Junwen ^{[1
]}

Zhang, Jin ^{[1
]}

Xu, Hengzhou ^{[1
]}

Cheng, Sen ^{[1
]}

Zhang, Yunsheng ^{[1
]}

Song, Wenjie ^{[1
]}

Liu, Fusheng ^{[1
]}

机构：

[1] Capital Med Univ, Beijing Tiantan Hosp, Beijing Lab Biomed Mat,Dept Neurosurg, Brain Tumor Res Ctr,Beijing Neurosurg Inst, Tiantan Xili 6, Beijing 100050, Peoples R China

来源：

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY | 2016年 / 142卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Fatty acid synthase; Glioma stem cells; Neovascularization; Vascular endothelial growth factor A; HUMAN BREAST-CANCER; STEM-LIKE CELLS; COLORECTAL-CANCER; ENDOTHELIAL-CELLS; UP-REGULATION; TUMOR-CELLS; BRAIN-TUMOR; ORLISTAT; ANGIOGENESIS; APOPTOSIS;

D O I：

10.1007/s00432-016-2249-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Fatty acids (FAs) are essential for membrane lipids biosynthesis and energy consumption in cancer cells. De novo FAs synthesis is catalyzed by fatty acid synthase (FASN), which is overexpressed and correlates with histological grade in glioma. Herein, we focused on the role of FASN in glioma neovascularization. The expression levels of FASN, Ki67 and CD34 were determined using immunohistochemistry (IHC). FASN specific-targeted shRNA and C75 were applied to evaluate the influence of FASN on glioma stem cell proliferation, migration and tube formation ability in vitro. An intracranial glioma model was established to study the effects of FASN on tumor growth and neovascularization in vivo. IHC staining showed that the expression level of FASN correlated with tumor grade, Ki67 levels and microvessels density (MVD) in human gliomas. Inhibition of FASN using shRNAs or C75 decreased tumor growth, prolonged the overall survival of xenograft mice and decreased MVD in brain tumor sections. Moreover, inhibition of FASN blocked hypoxia-inducible factor-1 alpha (HIF-1 alpha)/vascular endothelial growth factor A (VEGF-A) signaling and upregulated the anti-angiogenic isoform-VEGF(165)b. Our results suggest that FASN plays a pivotal role in glioma neovascularization, and inhibition of FASN may be a potential target for anti-angiogenic therapy for glioma.

引用

页码：2447 / 2459

页数：13

共 35 条

[1] Fatty acid synthase inhibitors are chemopreventive for mammary cancer in neu-N transgenic mice [J].