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RNAi-mediated gene silencing of vascular endothelial growth factor-C inhibits tumor lymphangiogenesis and growth of gastric cancer in vivo in mice

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Tumor Biology

Abstract

Overexpression of vascular endothelial growth factor-C (VEGF-C) has been implicated as a critical molecular signal in tumor development by promoting intratumoral lymphangiogenesis. The aim of this study was to explore whether small hairpin RNA (shRNA) targeting VEGF-C could inhibit gastric cancer lymphangiogenesis and tumor growth. Plasmid-mediated expression of VEGF-C–shRNA was employed to silence VEGF-C gene expression in human SGC-7901 cell lines. The inhibition of the target gene expression was quantified by real-time quantitative polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay. In vitro, the cell viability was determined by MTT assay, flow cytometry analysis, and migration assay. After VEGF-C knockdown was confirmed, the stable cells were inoculated into nude mice. Tumor growth, lymph vessel density (LVD), and microvascular density were compared for mice administered either VEGF-C–shRNA or control. VEGF-C–shRNA causes effective and specific downregulation of VEGF-C expression (P < 0.05). The migration activity of SGC-7901 cells was attenuated in vitro (P < 0.05). Tumor growth rate and LVD was suppressed in vivo (P < 0.05). VEGF-C–shRNA effectively suppressed gastric cancer cell migration in vivo, retards tumorigenicity, and lymphangiogenesis in nude mice.

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Acknowledgments

This project is supported by the National Natural Science Foundation of China (grant no.: 30960371).

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Authors and Affiliations

  1. Department of Surgery, Ningxia Medical University, Yingchuan, People’s Republic of China

    Jibin Yao, Yaoxing Duan & Yongbin Zhang

  2. Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou, 730000, People’s Republic of China

    Mingxu Da & Tiankang Guo

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  1. Jibin Yao
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  2. Mingxu Da
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  3. Tiankang Guo
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  4. Yaoxing Duan
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  5. Yongbin Zhang
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Correspondence to Mingxu Da.

Additional information

Jibin Yao and Mingxu Da contributed equally to this work.

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Yao, J., Da, M., Guo, T. et al. RNAi-mediated gene silencing of vascular endothelial growth factor-C inhibits tumor lymphangiogenesis and growth of gastric cancer in vivo in mice. Tumor Biol. 34, 1493–1501 (2013). https://doi.org/10.1007/s13277-013-0674-6

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  • DOI: https://doi.org/10.1007/s13277-013-0674-6

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