Ribozyme-mediated reversal of the multidrug-resistant phenotype

作者: K. J. Scanlon , H. Ishida , M. Kashani-Sabet

DOI: 10.1073/PNAS.91.23.11123

关键词: TransfectionP-glycoproteinMultiple drug resistanceMolecular biologyPhenotypeRegulation of gene expressionBiologyHammerhead ribozymeGeneRibozyme

摘要: Abstract This study examined the effects of suppressing c-fos oncogene expression on multidrug resistance (MDR). A2780S human ovarian carcinoma cells with to actinomycin D were isolated and resultant A2780AD exhibited MDR phenotype. A hammerhead ribozyme designed cleave fos RNA cloned into pMAMneo plasmid was transfected cells. Induction resulted in decreased c-fos, as well that gene (mdr-1), c-jun, mutant p53. The transformants displayed altered morphology restored sensitivity chemotherapeutic agents comprising An anti-mdr separately expressed efficiently degraded mdr-1 mRNA. However, reversal phenotype by occurred one-fourth rapidly induced anti-fos ribozyme. These results reinforce central role played drug through its participation signal transduction pathways.