Inhibition of Raf-1 protein kinase by antisense phosphorothioate oligodeoxyribonucleotide is associated with sensitization of human laryngeal squamous carcinoma cells to gamma radiation.
BACKGROUND
Previous studies suggest a central role for Raf-1 protein kinase in mitogenic and radiation damage responsive signaling pathways.


OBJECTIVE
Here we report that the expression and enzymatic activity of Raf-1 protein are inhibited in SQ-20B cells exposed to raf antisense oligodeoxyribonucleotide (As-ODNs) directed against the translation initiation site of human c-raf-1 cDNA. In contrast, treatment of SQ-20B cells with an equimolar concentration of raf sense oligodeoxy-ribonucleotide (S-ODNs) had no effect on the expression and activity of Raf-1.


RESULTS
We have observed radiosensitization of raf As-ODNs-treated SQ-20B cells. The dose modifying factor of As-ODNs treatment was approximately 1.4.


CONCLUSIONS
These studies demonstrate that raf As-ODNs is a DNA sequence-specific radiosensitizer that may have potential for use in the radiation therapy of cancers.
Soldatenkov
V A
VA
Department of Radiation Medicine, Lombardi Cancer Center, Georgetown University Medical Center, Washington, D.C. 20007, USA.
Dritschilo
A
A
Wang
F H
FH
Olah
Z
Z
Anderson
W B
WB
Kasid
U
U
D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005720:Gamma Rays / Q000627:therapeutic use; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D019908:Proto-Oncogene Proteins c-raf; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D013379:Substrate Specificity; D013873:Thionucleotides / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D011838:Radiation-Sensitizing Agents; D013873:Thionucleotides; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf