Glucocorticoids enhance cytotoxicity of cisplatin via suppression of NF-κB activation in the glucocorticoid receptor-rich human cervical carcinoma cell line SiHa
Journal
Journal of Endocrinology
Journal Volume
188
Journal Issue
2
Pages
311-319
Date Issued
2006
Author(s)
Abstract
Glucocorticoids (GCs) are commonly co-administered with cisplatin in the treatment of patients with carcinomas to prevent drug-induced allergic reaction, nausea and vomiting. Although GC receptor (GR) is ubiquitous in carcinoma cells and has been linked to signal transduction pathways pertinent to cell growth and apoptosis, little is known regarding the possible effect of GC on the chemosensitivity of carcinomas. Our previous study demonstrated that dexamethasone (DEX) enhances the cytotoxicity to cisplatin in a GR-rich human cervical carcinoma cell line, SiHa. In this study, we found that this cisplatin cytotoxicity-enhancing effect of DEX correlated well with its effect on abrogating the cisplatin-induced activation of nuclear factor kappa B (NF-κB). RU486, a structural homologue of DEX, partially reversed this cytotoxicity-enhancing effect of DEX, a finding consistent with the well-known partial reversing effect of RU486 on DEX-induced NF-κB suppression. Furthermore, expression of a dominant-negative truncated IκBα gene in SiHa cells completely abolished the cisplatin cytotoxicity-enhancing effect of DEX. Our data suggest that the specific action of DEX on GR may enhance the cytotoxicity of cisplatin in selected GR-rich cancer cells by suppressing NF-κB activation. ? 2006 Society for Endocrinology.
SDGs
Other Subjects
cisplatin; dexamethasone; glucocorticoid; glucocorticoid receptor; I kappa B alpha; immunoglobulin enhancer binding protein; mifepristone; article; cancer cell culture; cancer inhibition; cell selection; controlled study; correlation analysis; cytotoxicity; enzyme activation; enzyme inhibition; female; gene expression; human; human cell; priority journal; structural homology; uterine cervix carcinoma; Anti-Inflammatory Agents; Antineoplastic Agents; bcl-2-Associated X Protein; Cell Cycle Proteins; Cell Line, Tumor; Cisplatin; Dexamethasone; Gene Expression Regulation; Hormone Antagonists; Humans; Immediate-Early Proteins; Mifepristone; Mitogen-Activated Protein Kinases; NF-kappa B; Phosphoprotein Phosphatase; Protein-Tyrosine-Phosphatase; Proto-Oncogene Proteins c-bcl-2; Receptors, Glucocorticoid
Type
journal article