[Reversal of drug resistance in human cancer cells by anti-oncogenes].
The demonstration that RNA can be cleaved by cis ribozyme (catalytic RNAs, RNA enzymes) has potentially important therapeutic implications. Ribozymes are effective for modulation of gene expression because of their simple structure, site-specific cleavage activity, and catalytic potential. The targets of ribozyme-mediated gene modulation have ranged from cancer cells to foreign genes that cause infectious diseases. Additional target sites for ribozymes are in initial phases of development and design. Ribozymes have been targeted against myriad genes, including oncogenes (ras, BCR-ABL) and drug resistance genes (MDR-1, c-fos). These ribozymes have cleaved the target RNAs in culture system and developed to the in vivo system. We reported that fos ribozyme has altered the expression of c-fos and DNA repair genes in drug resistance cancer cells, and reversed the sensitivity to cisplatin. Furthermore, we have developed high efficiency by the transfer system in vivo.
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Dept. of Clinical and Laboratory Medicine, Tohoku University, School of Medicine.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D016761:Oncogene Proteins v-fos; D016337:RNA, Catalytic; D002945:Cisplatin