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Research Paper
Indomethacin Enhances the Cytotoxicity of Recombinant Human Lymphotoxin α on Tumor Cells by Suppressing NF-κB Signaling
Yijun Shen, Tong Yang, Jing Wang, Qing Xu, Rong Li, Wei Pan, Gang Li, Zheng Wang, Jingwei Tan, Jinsong Wu, Fang Wu, Luochun Wang and Yanjun Liu
volume 6 | issue 9
September 2007Pages: 1428 - 1433
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Indomethacin is widely used to treat inflammatory and prevent adverse events which are frequently accrues 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 (NF-κB) by inhibiting phosphorylation and degradation of IκB-α. In addition, indomethacin decreased the expression of NF-κB-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.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.