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MicroRNAs targeting mutant K-ras by electrotransfer inhibit human colorectal adenocarcinoma cell growth in vitro and in vivo

Cancer Gene Therapy volume 17, pages 409–419 (2010)Cite this article

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Abstract

Mutations of K-ras have been found in 30–60% of colorectal carcinomas and are believed to be associated with tumor initiation, tumor progression and metastasis formation. Therefore, silencing of mutant K-ras expression has become an attractive therapeutic strategy for colorectal cancer treatment. The aim of our study was to investigate the effect of microRNA (miRNA) molecules directed against K-ras (miRNA-K-ras) on K-ras expression level and the growth of colorectal carcinoma cell line LoVo in vitro and in vivo. In addition, we evaluated electroporation as a gene delivery method for transfection of LoVo cells and tumors with plasmid DNA encoding miRNA-K-ras (pmiRNA-K-ras). Results of our study indicated that miRNAs targeting K-ras efficiently reduced K-ras expression and cell survival after in vitro electrotransfection of LoVo cells with pmiRNA-K-ras. In vivo, electroporation has proven to be a simple and efficient delivery method for local administration of pmiRNA-K-ras molecules into LoVo tumors. This therapy shows pronounced antitumor effectiveness and has no side effects. The obtained results demonstrate that electrogene therapy with miRNA-K-ras molecules can be potential therapeutic strategy for treatment of colorectal cancers harboring K-ras mutations.

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Acknowledgements

We acknowledge the financial support from the state budget by the Slovenian Research Agency (programme No. P3-0003; project No. J3-7044 and J3-0485).

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Authors and Affiliations

  1. Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

    S Vidic, B Markelc, G Sersa, U Kamensek, G Tevz, S Kranjc & M Cemazar

  2. University of Primorska, College of Health Care Isola, Izola, Slovenia

    A Coer & M Cemazar

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  1. S Vidic
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Correspondence to M Cemazar.

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Vidic, S., Markelc, B., Sersa, G. et al. MicroRNAs targeting mutant K-ras by electrotransfer inhibit human colorectal adenocarcinoma cell growth in vitro and in vivo. Cancer Gene Ther 17, 409–419 (2010). https://doi.org/10.1038/cgt.2009.87

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  • DOI: https://doi.org/10.1038/cgt.2009.87

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