Ribozyme as an approach for growth suppression of human pancreatic cancer.

Abstract

Ribozymes (catalytic RNAs, RNA enzymes) are effective modulators of gene expression because of their simple structure, site-specific cleavage activity, and catalytic potential, and have potentially important implications for cancer gene therapy. Point mutations in the K-ras oncogene are found in approx 90% of human pancreatic carcinomas, and can be used as potential targets for specific ribozyme-mediated reversal of the malignant phenotype. In this study, we focused on in vitro manipulation of ribozyme targeting of the mutated K-ras oncogene in a human pancreatic carcinoma cell line. We evaluated the efficacy of an anti-K-ras hammerhead ribozyme targeted against GUU-mutated codon 12 of the K-ras gene in cultured pancreatic carcinoma cell lines. The anti-K-ras ribozyme significantly reduced cellular K-ras mRNA level (GUU-mutated codon 12) when the ribozyme was transfected into the Capan-1 pancreatic carcinoma cells. The ribozyme inhibited proliferation of the transfected Capan-1 cells. These results suggested that this ribozyme is capable of reversing the malignant phenotype in human pancreatic carcinoma cells.

• Authors: H Kijima, K J Scanlon
• Journal: Molecular biotechnology (Mol Biotechnol) Vol. 14 Issue 1 Pg. 59-72 (Jan 2000) ISSN: 1073-6085 [Print] United States
• PMID: 10911615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Catalytic

Topics

• Cell Division (genetics)
• Cloning, Molecular
• Drug Screening Assays, Antitumor
• Gene Expression Regulation, Neoplastic
• Genes, ras
• Genetic Therapy (methods)
• Humans
• Mutation
• Pancreatic Neoplasms (genetics, therapy)
• RNA, Catalytic (genetics)
• Transfection
• Tumor Cells, Cultured