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

  • Original Article – Cancer Research
  • Published:
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Abstract

Purpose

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.

Methods

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.

Results

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-1α (HIF-1α)/vascular endothelial growth factor A (VEGF-A) signaling and upregulated the anti-angiogenic isoform-VEGF165b.

Conclusion

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.

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Acknowledgments

We thank Prof. L Luo, GL Li and L Xu (Pathological Department, Beijing Neurosurgical Institute) for evaluating human and mouse glioma specimens.

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 81372354, 81302186), the Beijing Municipal Natural Science Foundation (No. 7151002), the Beijing Health System High-level Personnel Building Foundation (No. 2013-3-018), the Beijing Laboratory of Biomedical Materials Foundation (PXM2014_014226_000005) and the Beijing Municipal Administration of Hospitals’ Youth Program (No. QML20150505).

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Authors and Affiliations

  1. Brain Tumor Research Center, Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing Laboratory of Biomedical Materials, Tiantan Xili 6, Dongcheng District, Beijing, 100050, People’s Republic of China

    Yiqiang Zhou, Guishan Jin, Ruifang Mi, Junwen Zhang, Jin Zhang, Hengzhou Xu, Sen Cheng, Yunsheng Zhang, Wenjie Song & Fusheng Liu

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  1. Yiqiang Zhou
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  2. Guishan Jin
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  7. Sen Cheng
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  10. Fusheng Liu
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Corresponding author

Correspondence to Fusheng Liu.

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Conflict of interest

The author declares no competing interest.

Ethics approval

The glioma tissue collection was approved by the Institutional Review Board of Beijing Tiantan Hospital affiliated to Capital Medical University. The Experimental Animal Ethics Committee of Beijing Neurosurgical Institute approved the use of laboratory animals. All animal experiments followed the NIH Guide for the Care and Use of Laboratory Animals (No. 2014-02016).

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Informed consents were prospectively obtained from all individual participants in this study.

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Zhou, Y., Jin, G., Mi, R. et al. Inhibition of fatty acid synthase suppresses neovascularization via regulating the expression of VEGF-A in glioma. J Cancer Res Clin Oncol 142, 2447–2459 (2016). https://doi.org/10.1007/s00432-016-2249-6

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  • DOI: https://doi.org/10.1007/s00432-016-2249-6

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