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Nanoparticle-delivered VEGF-silencing cassette and suicide gene expression cassettes inhibit colon carcinoma growth in vitro and in vivo

  • Research Article
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Tumor Biology

Abstract

The strategies for tumor-specific expression of suicide genes and target tumor angiogenesis have been tested in tumors. However, the anti-tumor efficacy of the combination of these two strategies, particularly, delivering suicide gene and anti-angiogenesis agent by nanoparticles, has not yet been evaluated in colon carcinoma. We constructed a cassette to silence VEGF-A expression and express a fused yCDglyTK gene driven by tumor-specific promoter (shVEGF-CDTK). The DNA carrying shVEGF-CDTK was delivered into colon carcinoma cells by calcium phosphate nanoparticles (CPNPs). Cell proliferation was measured by MTT assay, and apoptosis was detected by flow cytometry. The anti-tumor effect of the combined cassette was tested in xenograft animal model. With 5-fluorocytosine (5-FC), CPNP-delivered shVEGF-CDTK DNA (CPNP-shVEGF-CDTK) showed high expression of fused yCDglyTK gene and effectively silenced VEGF-A expression in vitro and in vivo, which significantly inhibited colon carcinoma cell proliferation and induced apoptosis in vitro. With 5-FC, the systemic delivery of CPNP-shVEGF-CDTK significantly inhibited tumor growth in the colon carcinoma xenograft animal model. The combined cassette is obviously effective in inhibiting tumor cell proliferation and inducing apoptosis in vitro and tumor growth in vivo than the CPNP-shVEGF or CPNP-CDTK alone. The combination of VEGF-A-silencing and tumor-specific expression of suicide gene is an effective strategy for colon carcinoma treatment.

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Acknowledgments

This work has been supported by the Chinese National Natural Science Foundation (grant no. 30800518) and the New Teachers of Doctor Fund Project of Ministry of Education (grant no. 200805331090).

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Authors and Affiliations

  1. Department of Gastroenterology, Xiangya Hospital, Changsha, 410008, China

    Aimin Leng, Jing Yang, Ting Liu, Jianfang Cui, Xiu-hua Li, Yanan Zhu & Ting Xiong

  2. School of Biological Science and Technology, Central South University, Changsha, 410008, China

    Yuxiang Chen

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  1. Aimin Leng
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  2. Jing Yang
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  3. Ting Liu
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  4. Jianfang Cui
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  6. Yanan Zhu
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  7. Ting Xiong
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  8. Yuxiang Chen
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Correspondence to Yuxiang Chen.

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Leng, A., Yang, J., Liu, T. et al. Nanoparticle-delivered VEGF-silencing cassette and suicide gene expression cassettes inhibit colon carcinoma growth in vitro and in vivo. Tumor Biol. 32, 1103–1111 (2011). https://doi.org/10.1007/s13277-011-0210-5

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  • DOI: https://doi.org/10.1007/s13277-011-0210-5

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