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VEGF is essential for the growth and migration of human hepatocellular carcinoma cells

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Abstract

Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF induces new vessel formation and tumor growth by inducing mitogenesis and chemotaxis of normal endothelial cells and increasing vascular permeability. However, little is known about VEGF function in the proliferation, survival or migration of hepatocellular carcinoma cells (HCC). In the present study, we have found that VEGF receptors are expressed in HCC line BEL7402 and human HCC specimens. Importantly, VEGF receptor expression correlates with the development of the carcinoma. By using a comprehensive approaches including TUNEL assay, transwell and wound healing assays, migration and invasion assays, adhesion assay, western blot and quantitative RT-PCR, we have shown that knockdown of VEGF165 expression by shRNA inhibits the proliferation, migration, survival and adhesion ability of BEL7402. Knockdown of VEGF165 decreased the expression of NF-κB p65 and PKCα while increased the expression of p53 signaling molecules, suggesting that VEGF functions in HCC proliferation and migration are mediated by P65, PKCα and/or p53.

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Acknowledgments

This study was supported by grants from National natural Science Foundation of China (81170095; 30700306), Hubei Health Department Science Foundation (JX5B24), Hubei Education Department Science Foundation (T2008010,T201112, Q200524003), China; And National Institutes of Health (HL093429 and HL107526).

Conflicts of interest

All authors have read and approved the manuscript, and there is no ethical problem or conflict of interest.

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Authors and Affiliations

  1. Department of Cardiology and Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Lei Zhang, Jia-Ning Wang, Jun-Ming Tang, Xia Kong, Jian-Ye Yang, Fei Zheng, Ling-Yun Guo & Yong-Zhang Huang

  2. Key Laboratory of Human Embryonic Stem Cell of Hubei Province, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Lei Zhang, Jia-Ning Wang, Jun-Ming Tang, Xia Kong, Jian-Ye Yang, Fei Zheng, Ling-Yun Guo & Yong-Zhang Huang

  3. Department of Physiology, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Jun-Ming Tang

  4. Department of Pathology, Renmin Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Li Zhang, Lin Tian, Shu-Fen Cao, Chang-Hai Tuo & Hong-Li Guo

  5. Department of Physiology & Pharmacology, The University of Georgia, Athens, GA, 30602, USA

    Shi-You Chen

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  1. Lei Zhang
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Correspondence to Jia-Ning Wang.

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Zhang, L., Wang, JN., Tang, JM. et al. VEGF is essential for the growth and migration of human hepatocellular carcinoma cells. Mol Biol Rep 39, 5085–5093 (2012). https://doi.org/10.1007/s11033-011-1304-2

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  • DOI: https://doi.org/10.1007/s11033-011-1304-2

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