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Objective To investigate the specifically efficacy of antisense RNA rescue targetting the mutant exon 8 of p53 gene (ASp53exon8’RNA) and explore its possible gene therapeutic implications in combination with wild-type p53 gene(WT-p53). Methods The single strand antisense transcription system containing mt-p53 exon8 sequence was constructed. In vitro, MDA-MB-231 cells and transfected WTp53-231 cells which stably expressing WT-p53 were exposed to cationic liposome -ASp53exon8’RNA,and the growth inhibition rate, expression of p53, and induction of apoptosis were measured 48 hours later. In vivo, the MDA-MB-231 tumor transplanted into nude mice grew to 6 to 8 mm in diameter. Following growth of the tumor to this size, liposome-ASp53exon8’RNA alone, or combined with liposome- WT-p53 were locally applied to the peripheral tumor (day 0) and then applied once every 3 days for a total of seven times (day 21). ResultsIn vitro, hybridization signals were manifested in transfected cell cytoplasm. ASp53exon8’RNA exhibited inhibitory effects on tumor cell growth and expression of p53, as well as increased apoptotic rates. Furthermore, synergistic effects were observed when combined with WT-p53. In nude mouse models, ASp53exon8’RNA alone inhibited tumor growth and induced tumor necrosis. Also, combined treatments showed synergistical effects without any apparent increase in toxicity. Conclusions ASp53exon8’RNA can specifically block mt-p53 gene expression and synergistically suppress cell growth in combination with WT-p53, which may serve as effective strategy for human cancer treatment.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA