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Inhibition of cervical cancer cell growth in vitro and in vivo with dual shRNAs

Cancer Gene Therapy volume 18, pages 219–227 (2011)Cite this article

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Abstract

RNA interference (RNAi)-based gene silencing is widely used in laboratories for gene function studies and also holds a great promise for developing treatments for diseases. However, in vivo delivery of RNAi therapy remains a key issue. Lentiviral vectors have been employed for stable gene transfer and gene therapy and therefore are expected to deliver a stable and durable RNAi therapy. But this does not seem to be true in some disease models. Here, we showed that lentivirus delivered short-hairpin RNA (shRNA) against human papillomavirus (HPV) E6/E7 oncogenes were effective for only 2 weeks in a cervical cancer model. However, using this vector to carry two copies of the same shRNA or two shRNAs targeting at two different but closely related genes (HPV E6 and vascular endothelial growth factor) was more effective at silencing the gene targets and inhibiting cell or even tumor growth than their single shRNA counterparts. The cancer cells treated with dual shRNA were also more sensitive to chemotherapeutic drugs than single shRNA-treated cells. These results suggest that a multi-shRNA strategy may be a more attractive approach for developing an RNAi therapy for this cancer.

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Abbreviations

RNAi:

RNA interference

shRNA:

short hairpin RNA

HPV:

human papillomavirus

siRNA:

short interfering RNA

VEGF:

vascular endothelial growth factor

LV:

lentiviral vector

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Acknowledgements

We thank Dr Ibtissam Abdul Jabbar for her technical support of cell sorting. Funding sources are NHMRC project grant (NM, GL) and NHMRC Peter Doherty Fellowship (WG) and Early Career Researcher Grant (WG) of the University of Queensland, Brisbane, Australia and the Australian Cancer Research Foundation.

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Authors and Affiliations

  1. UQ Diamantina Institute, The University of Queensland, Brisbane, Australia

    W Gu, E Payne, M Burgess & N A J McMillan

  2. College of Life Science and Technology, Xinjiang University, Urumqi, P.R. China

    S Sun

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Correspondence to W Gu or N A J McMillan.

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Gu, W., Payne, E., Sun, S. et al. Inhibition of cervical cancer cell growth in vitro and in vivo with dual shRNAs. Cancer Gene Ther 18, 219–227 (2011). https://doi.org/10.1038/cgt.2010.72

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