Ribozyme as an approach for growth suppression of human pancreatic cancer.
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.
Department of Pathology, Tokai University School of Medicine, Isehara, Kanagawa. hkijima@is.icc.u-tokai.ac.jp
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D002455:Cell Division / Q000235:genetics; D003001:Cloning, Molecular; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000628:therapy*; D016337:RNA, Catalytic / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016337:RNA, Catalytic