Oligonucleotides protect cells from the cytotoxicity of several anti-cancer chemotherapeutic drugs.

The possibility of inhibiting gene expression with antisense oligonucleotides (AS ODNs) in combination with more conventional chemotherapy is a very attractive modality in oncology. However, possible interaction between the ODN and drug must be considered. Here we show that ODNs protect cells from the cytostatic/cytotoxic action of actinomycin D (AMD), adriamycin, daunomycin or quinacrine, but not mitomycin, camptothecin, vincristine, cisplatin, etoposide (VP-16) or cycloheximide. The cytoprotective effect depends on ODN length as well as ability to interact directly with the cytotoxic drug and is only slightly sequence selective.