This work was supported by Sanofi-Aventis (GIA-10095). The sponsor was involved in the review and approval of this manuscript. However, the sponsor was not involved in the design and conduct of the study. The sponsor was also not involved in the collection, analysis, and interpretation of the data and preparation of the manuscript. Dr. Yoo had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Head and Neck
XRP6258-induced gene expression patterns in head and neck cancer carcinoma†
Version of Record online: 20 APR 2010
Copyright © 2010 The American Laryngological, Rhinological, and Otological Society, Inc.
Volume 120, Issue 6, pages 1114–1119, June 2010
How to Cite
Yoo, G. H., Kafri, Z., Ensley, J. F., Lonardo, F., Kim, H., Folbe, A. J., Won, J., Stevens, T. and Lin, H.-S. (2010), XRP6258-induced gene expression patterns in head and neck cancer carcinoma. The Laryngoscope, 120: 1114–1119. doi: 10.1002/lary.20559
- Issue online: 21 MAY 2010
- Version of Record online: 20 APR 2010
- Manuscript Accepted: 11 FEB 2009
- Cell cycle;
- novel taxoid
XRP6258 is a novel taxoid, which has antitumor activity in preclinical mouse orthotopic and human xenograft cancer models. However, limited XRP6258 studies have been performed in head and neck squamous cell carcinoma cells (HNSCC). The objective of this study is to identify the antitumor activity of XRP6258 in HNSCC cell line models.
HNSCC cells (HN30 and HN12) were exposed to either XRP6258 or docetaxel. XRP6258-induced growth suppression, cell cycle arrest and apoptosis were measured. Further, XRP6258-induced expression patterns of selected genes were compared to docetaxel-induced expression patterns using Western blot analysis.
XRP6258 suppressed proliferation and induced G2M arrest and apoptosis in both of the cell lines tested. XRP6258 and docetaxel produced similar alteration in the expression of cell cycle regulators, such as cyclin A and cyclin B1. The expression of E2F and EGFR were decreased in both XRP6258 and docetaxel-treated HNSCC cells. Finally, XRP6258 induced a greater level of bcl2 phosphorylation than docetaxel in HN12 cell line.
XRP6258 appeared to have a similar mechanism of action as docetaxel in the two HNSCC cell lines studied. XRP6258 induced cell cycle arrest, growth suppression, and apoptosis by altering gene expression patterns similar to that induced by docetaxel. These preclinical experiments suggest that XRP6258 may be useful in treating HNSCC, and the aforementioned genes can potentially be used as surrogate endpoint biomarkers. Laryngoscope, 120:1114–1119, 2010