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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Molecular Cancer 1/2012

Gene therapy for colorectal cancer by an oncolytic adenovirus that targets loss of the insulin-like growth factor 2 imprinting system

Zeitschrift:
Molecular Cancer > Ausgabe 1/2012
Autoren:
Zhen-Lin Nie, Yu-Qin Pan, Bang-Shun He, Ling Gu, Li-Ping Chen, Rui Li, Ye-Qiong Xu, Tian-Yi Gao, Guo-Qi Song, Andrew R Hoffman, Shu-Kui Wang, Ji-Fan Hu
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1476-4598-11-86) contains supplementary material, which is available to authorized users.
Zhen-Lin Nie, Yu-Qin Pan contributed equally to this work.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

SW, YP, and ZN designed the study and wrote the protocols. ZN performed most of the experiments. BH, LG, and LC contributed to administrative, technical or material support. RL, YX, and TG managed the literature searches and analyses. GS undertook the statistical analysis. ZN drafted the manuscript. AH and JH provided critiques of the manuscript. All authors read and approved the final manuscript.

Abstract

Background

Colorectal cancer is one of the most common malignant tumors worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality observed in human colorectal neoplasms. Our aim was to investigate the feasibility of using the IGF2 imprinting system for targeted gene therapy of colorectal cancer.

Results

We constructed a novel oncolytic adenovirus, Ad315-E1A, and a replication-deficient recombinant adenovirus, Ad315-EGFP, driven by the IGF2 imprinting system by inserting the H19 promoter, CCCTC binding factor, enhancer, human adenovirus early region 1A (E1A) and enhanced green fluorescent protein (EGFP) reporter gene into a pDC-315 shuttle plasmid. Cell lines with IGF2 LOI (HCT-8 and HT-29), which were infected with Ad315-EGFP, produced EGFP. However, no EGFP was produced in cell lines with maintenance of imprinting (HCT116 and GES-1). We found that Ad315-E1A significantly decreased cell viability and induced apoptosis only in LOI cell lines in vitro. In addition, mice bearing HCT-8-xenografted tumors, which received intratumoral administration of the oncolytic adenovirus, showed significantly reduced tumor growth and enhanced survival.

Conclusions

Our recombinant oncolytic virus targeting the IGF2 LOI system inhibits LOI cell growth in vitro and in vivo, and provides a novel approach for targeted gene therapy.
Zusatzmaterial
Authors’ original file for figure 1
12943_2012_1070_MOESM1_ESM.pdf
Authors’ original file for figure 2
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Authors’ original file for figure 3
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Authors’ original file for figure 4
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Authors’ original file for figure 5
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Authors’ original file for figure 6
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Literatur
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