Stable inhibition of nuclear factor kappaB in cancer cells does not increase sensitivity to cytotoxic drugs.
Several reports indicated that nuclear factor kappaB (NF-kappaB) activation by cytokines, cytotoxic drugs, or ionizing radiation protects cells against apoptosis. Therefore, we investigated the consequence of NF-kappaB inhibition on the efficiency of antineoplastic agents. HPB, HCT116, MCF7, and OVCAR-3 cells stably expressing a dominant negative IkappaBalpha inhibitor showed a decreased NF-kappaB activation following treatment with tumor necrosis factor a and various chemotherapeutic agents. However, there was no difference in survival between parental cells and cells expressing mutated IkappaBalpha. These studies suggest that, at least in these cell lines, stable NF-kappaB inhibition did not modify the response to cytotoxic drugs.
Laboratory of Medical Chemistry/Medical Oncology, University of Liège, Belgium.
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Bentires-Alj
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Hellin
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Ameyar
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S
Chouaib
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MP
Merville
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Bours
D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha