Indomethacin enhances the cytotoxicity of recombinant human lymphotoxin α on tumor cells by suppressing NFκB signaling

Abstract

Indomethacin is widely used to treat inflammatory and prevent adverse events which frequently accrue in biotherapy. In phase I clinical trial of recombinant human lymphotoxin α (rhLTα), indomethacin was premedicated to alleviate chill and fever. However, it is unknown whether indomethacin influences the therapeutic efficacy of rhLTα. In this study we found that pre-treatment with low dose of indomethacin enhanced the cytotoxicity of rhLTα and/or cisplatin/adriamycin on human tumor cells. Further investigation demonstrated that indomethacin dose-dependently suppressed the activation of nuclear factor kappa B (NFκB) by inhibiting phosphorylation and degradation of IκBα. In addition, indomethacin decreased the expression of NFκB-regulated gene products involved in rhLTα-induced anti-apoptosis (XIAP, cFLIP and cIAP-1), which may explain its sensitization of tumor cells to rhLTα and/or cisplatin/adriamycin. ©2007 Landes Bioscience.