ANTITUMOR-ACTIVITY OF A PHOSPHOROTHIOATE ANTISENSE OLIGODEOXYNUCLEOTIDE TARGETED AGAINST C-RAF KINASE

Citation
Bp. Monia et al., ANTITUMOR-ACTIVITY OF A PHOSPHOROTHIOATE ANTISENSE OLIGODEOXYNUCLEOTIDE TARGETED AGAINST C-RAF KINASE, Nature medicine, 2(6), 1996, pp. 668-675
Citations number
48
Categorie Soggetti
Medicine, Research & Experimental",Biology,"Cell Biology
Journal title
ISSN journal
10788956
Volume
2
Issue
6
Year of publication
1996
Pages
668 - 675
Database
ISI
SICI code
1078-8956(1996)2:6<668:AOAPAO>2.0.ZU;2-D
Abstract
Substantial evidence exists supporting a direct role for raf kinases i n the development and maintenance of certain human malignancies. Here we test the potential of phosphorothioate antisense oligodeoxynucleoti des targeted against human C-raf-l kinase to specifically inhibit C-ra f-l kinase gene expression and tumor progression in cell culture and i n vivo, using human tumor xenograft mouse models. Treatment of human t umor cells with appropriate phosphorothioate antisense oligodeoxynucle otides led to specific inhibition of C-raf kinase gene expression in c ell culture and in vivo at well-tolerated doses. Moreover, oligodeoxyn ucleotide treatment resulted in potent antiproliferative effects in ce ll culture and potent antitumor effects in vivo against a variety of t umor types that were highly consistent with an antisense mechanism of action for these compounds. These studies strongly suggest that antise nse inhibitors targeted against C-raf-l kinase may be of considerable value as antineoplastic agents that display activity against a wide sp ectrum of tumor types at well-tolerated doses.