XRP6258-induced gene expression patterns in head and neck cancer carcinoma.
OBJECTIVE
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.


METHODS
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.


RESULTS
XRP6258 suppressed proliferation and induced G(2)M 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.


CONCLUSIONS
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.
Department of Otolaryngology-Head and Neck Surgery, John D. Dingell VA Medical Center, Detroit, Michigan, USA. yoo@med.wayne.edu
George H
GH
Yoo
Zyed
Z
Kafri
John F
JF
Ensley
Fulvio
F
Lonardo
Harold
H
Kim
Adam J
AJ
Folbe
Joshua
J
Won
Timothy
T
Stevens
Ho-Sheng
HS
Lin
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D019925:Cyclin A / Q000378:metabolism; D056744:Cyclin B1 / Q000378:metabolism; D000077143:Docetaxel; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D010766:Phosphorylation; D043823:Taxoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D019925:Cyclin A; D056744:Cyclin B1; D043823:Taxoids; C532412:XRP6258; D000077143:Docetaxel