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
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.