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Intratumoral delivery of shRNA targeting cyclin D1 attenuates pancreatic cancer growth

Cancer Gene Therapy volume 17, pages 325–333 (2010)Cite this article

Abstract

The aim of this study was to assess the biological consequences of cyclin D1 silencing in pancreatic cancer cells. A replication-defective lentivirus based small hairpin RNA (shRNA) system targeting cyclin D1 caused a marked reduction in cyclin D1 protein levels in ASPC-1 and BxPC3 pancreatic cancer cell lines in conjunction with decreased cell growth and invasiveness in vitro. Moreover, a single intratumoral injection of the recombinant lentivirus targeting cyclin D1 attenuated the growth of pre-existing tumors arising from two distinct cell lines. This attenuated growth correlated with decreased proliferation and angiogenesis, as well as attenuated vascular endothelial growth factor expression. It is concluded that lentivirus-delivered shRNA targeting cyclin D1 suppresses the growth, invasiveness, tumorigenicity and pro-angiogenic potential of human pancreatic cancer cells, thereby raising the possibility that intratumoral injections of viruses targeting cyclin D1 could provide a new therapeutic approach in pancreatic ductal adenocarcinoma.

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Acknowledgements

This study was supported, in part, by US Public Health Service Grant CA-101306 to MK; SD was the recipient of a post-doctoral fellowship award from the SASS Foundation for Medical Research.

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Authors and Affiliations

  1. Departments of Medicine, Pharmacology and Toxicology, Norris Cotton Center and Dartmouth Medical School, Lebanon, NH, USA

    S J Deharvengt, J R Gunn, S B Pickett & M Korc

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  1. S J Deharvengt
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  2. J R Gunn
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  3. S B Pickett
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  4. M Korc
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Correspondence to M Korc.

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Deharvengt, S., Gunn, J., Pickett, S. et al. Intratumoral delivery of shRNA targeting cyclin D1 attenuates pancreatic cancer growth. Cancer Gene Ther 17, 325–333 (2010). https://doi.org/10.1038/cgt.2009.75

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