作者: T Tokunaga , T Tsuchida , H Kijima , K Okamoto , Y Oshika
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摘要: Mutation of c-K-ras oncogene is an important step in progression colon cancer. We used a hammerhead ribozyme (KrasRz) against mutated K-ras gene transcripts (codon 12, GTT) to inactivate mutant function the cancer cell line SW480, harbouring gene. The β-actin promoter-driven KrasRz sequence (pHβ/KrasRz) was introduced into these cells (SW480/KrasRz), and we evaluated its effects on growth expression angiogenesis-related molecules (vascular endothelial factor thrombospondin) also estimated SW480/KrasRz. specifically efficiently cleaved mRNA but not wild-type vitro. SW480/KrasRz showed decreased rate under tissue culture conditions (P< 0.01, Dunnett’s test). xenotransplantability (XeSW480/KrasRz) significantly nude mice 0.05, Fisher’s exact Tumour volume xenografts XeSW480/KrasRz smaller than that XeSW480/DisKrasRz Gene VEGF suppressed SW480/KrasRz, while TSP1 enhanced. apoptosis-related features including nuclear condensation DNA fragmentation. These results suggested ribozyme-mediated inactivation induced suppression, apoptosis alteration angiogenic expression. © 2000 Cancer Research Campaign