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Aurora kinase A inhibition and paclitaxel as targeted combination therapy for head and neck squamous cell carcinoma
Author(s) -
Mazumdar Abhijit,
Henderson Ying C.,
ElNaggar Adel K.,
Sen Subrata,
Clayman Gary L.
Publication year - 2009
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.21007
Subject(s) - head and neck squamous cell carcinoma , cancer research , cell cycle , flow cytometry , cell growth , apoptosis , paclitaxel , cell , targeted therapy , immunohistochemistry , medicine , biology , pathology , cancer , head and neck cancer , microbiology and biotechnology , biochemistry , genetics
Abstract Background. Aurora kinase A (AURKA) is amplified with varying incidence in multiple human cancers including head and neck squamous cell carcinoma (HNSCC). We investigated whether AURKA is a potential therapeutic target in HNSCC. Methods. We conducted an immunohistochemical analysis of AURKA expression in paired normal and tumor samples ( n = 63). HNSCC cells treated with siRNA specific for AURKA were assessed for AURKA mRNA and protein expression levels by reverse transcriptase‐polymerase chain reaction and Western blot analysis. Tumor cells treated with siRNA and paclitaxel were assessed for cell proliferation by MTT assay and for cell cycle distribution by flow cytometry. Results. AURKA expression was higher in tumor than in adjacent normal in most (85%) of the samples analyzed. HNSCC cells and primary tumors revealed high expression levels of AURKA. Most primary tumors also showed high kinase activity of the enzyme. Targeted AURKA inhibition increased the sub‐G1 cell fraction, with a concomitant reduction in the G1 cell population, indicating induction of apoptosis and thus markedly suppressed proliferation of HNSCC cells. Combining siRNA‐induced AURKA inhibition with 5 to 10 n M paclitaxel synergistically enhanced apoptosis induction. Conclusion. AURKA is a potential therapeutic target for HNSCC. Further investigation of small‐molecule AURKA inhibitors as therapeutic agents is warranted. © 2008 Wiley Periodicals, Inc. Head Neck, 2009