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

Vidic, S., Markelc, B., Sersa, G., Coer, A., Kamensek, U., Tevz, G., Kranjc, S., & Cemazar, M. (2010) MicroRNAs targeting mutant K-ras by electrotransfer inhibit human colorectal adenocarcinoma cell growth in vitro and in vivo. Cancer Gene Therapy, 17(6), pp. 409-419.

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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. © 2010 Nature Publishing Group All rights reserved.

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ID Code: 73292
Item Type: Journal Article
Refereed: Yes
Keywords: Colorectal adenocarcinoma, Electroporation, K-ras, MiRNA, microRNA, plasmid DNA, animal experiment, animal model, antineoplastic activity, article, colon adenocarcinoma, controlled study, female, gene expression, gene mutation, gene targeting, gene therapy, human, human cell, in vitro study, in vivo study, mouse, nonhuman, oncogene K ras, priority journal, rectum carcinoma, Adenocarcinoma, Animals, Cell Line, Tumor, Cell Proliferation, Cell Survival, Colorectal Neoplasms, HT29 Cells, Humans, Mice, Mice, SCID, MicroRNAs, Mutation, ras Proteins, RNA, Small Interfering, Transfection, Tumor Burden, Xenograft Model Antitumor Assays
DOI: 10.1038/cgt.2009.87
ISSN: 09291903 (ISSN)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 08 Jul 2014 00:24
Last Modified: 09 Jul 2014 00:00

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