کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1935063 | 1050657 | 2009 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Specific repression of mutant K-RAS by 10–23 DNAzyme: Sensitizing cancer cell to anti-cancer therapies Specific repression of mutant K-RAS by 10–23 DNAzyme: Sensitizing cancer cell to anti-cancer therapies](/preview/png/1935063.png)
Point mutations of the Ras family are frequently found in human cancers at a prevalence rate of 30%. The most common mutation K-Ras(G12V), required for tumor proliferation, survival, and metastasis due to its constitutively active GTPase activity, has provided an ideal target for cancer therapy. 10–23 DNAzyme, an oligodeoxyribonucleotide-based ribonuclease consisting of a 15-nucleotide catalytical domain flanked by two target-specific complementary arms, has been shown to effectively cleave the target mRNA at purine–pyrimidine dinucleotide. Taking advantage of this specific property, 10–23 DNAzyme was designed to cleave mRNA of K-Ras(G12V)(GGU → GUU) at the GU dinucleotide while left the wild-type (WT) K-Ras mRNA intact. The K-Ras(G12V)-specific 10–23 DNAzyme was able to reduce K-Ras(G12V) at both mRNA and protein levels in SW480 cell carrying homozygous K-Ras(G12V). No effect was observed on the WT K-Ras in HEK cells. Although K-Ras(G12V)-specific DNAzymes alone did not inhibit proliferation of SW480 or HEK cells, pre-treatment of this DNAzyme sensitized the K-Ras(G12V) mutant cells to anti-cancer agents such as doxorubicin and radiation. These results offer a potential of using allele-specific 10–23 DNAzyme in combination with other cancer therapies to achieve better effectiveness on cancer treatment.
Journal: Biochemical and Biophysical Research Communications - Volume 378, Issue 2, 9 January 2009, Pages 230–234