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Inhibition of cervical cancer cell growth in vitro and in vivo with lentiviral-vector delivered short hairpin RNA targeting human papillomavirus E6 and E7 oncogenes

Cancer Gene Therapy volume 13, pages 1023–1032 (2006)Cite this article

Abstract

In this study, we investigated the suppressive effect of a short hairpin RNA delivered by a lentiviral vector (LV-shRNA) against human papillomavirus (HPV) type 18 E6 on the expression of the oncogenes E6 and E7 in cervical cancer HeLa cells both in vitro and in vivo. The LV-shRNA effectively delivered the shRNA to HeLa cells and lead to a dose-dependent reduction of E7 protein and the stabilization of E6 target proteins, p53 and p21. Low-dose infection of HeLa cells with LV-shRNA caused reduced cell growth and the induction of senescence, whereas a high-dose infection resulted in specific cell death via apoptosis. Transplant of HeLa cells infected with a low dose of LV-shRNA into Rag−/− mice significantly reduced the tumor weight, whereas transplant of cells infected with a high dose resulted in a complete loss of tumor growth. Systemic delivery of LV-shRNA into mice with established HeLa cell lung metastases led to a significant reduction in the number of tumor nodules. Our data collectively suggest that lentiviral delivery is an effective way to achieve stable suppression of E6/E7 oncogene expression and induce inhibition of tumor growth both in vitro and in vivo. These results encourage further investigation of this form of RNA interference as a promising treatment for cervical cancer.

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Acknowledgements

We thank Dr Brian Gabrielli for helpful suggestions for the study, and Drs Heather Beamish, Leonore de Boer and Ibtissam Abdul Jabbar for their technical help. This work was supported by grants from the National Health and Medical Research Council, the University of Queensland and the Princess Alexandra Hospital Research Foundation.

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  1. Cancer Biology Program, Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Brisbane, Australia

    W Gu, L Putral, K Hengst, K Minto, N A Saunders, G Leggatt & N A J McMillan

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  1. W Gu
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  2. L Putral
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Correspondence to N A J McMillan.

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Gu, W., Putral, L., Hengst, K. et al. Inhibition of cervical cancer cell growth in vitro and in vivo with lentiviral-vector delivered short hairpin RNA targeting human papillomavirus E6 and E7 oncogenes. Cancer Gene Ther 13, 1023–1032 (2006). https://doi.org/10.1038/sj.cgt.7700971

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