Adriamycin activates NF-κB in human lung carcinoma cells by IκBα degradation

The aim of this study was to investigate the effect of adriamycin (ADR) in signaling activation of NF-κB in ADR-sensitive and -resistant GLC4 human small-cell lung carcinoma. ADR activated NF-κB only in ADR-sensitive GLC4 cells in a time- and dose-dependant manner by stimulating IκBα degradation after 4 h. Activation of NF-κB in response to tumor necrosis factor was intact in both cell lines. Topoisomerase II, a target for a number of chemotherapeutic agents, was depleted in both types of GLC4 cells after ADR treatment, suggesting the stabilization of transient DNA–topoisomerase II complexes. Another transcription factor, Sp1, was activated by ADR, demonstrating the nonspecificity of NF-κB activation in ADR-sensitive GLC4 cells. These findings indicated that resistance to ADR in ADR-sensitive GLC4 cells did not involve the NF-κB transcription factor.