期刊
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK
卷 31, 期 5, 页码 625-634出版社
WILEY
DOI: 10.1002/hed.21007
关键词
HNSCC; AURKA; paclitaxel; combination therapy; antiproliferation
资金
- National Institutes of Health Independent Award [R01 DE-13954, R01CA89716]
- National Institutes of Health Specialized Program of Research Excellence [1P50-CA-97007]
- National Cancer Institute Cancer Center Support grant [5P30 CA 16672]
- Michael A. O'Bannon Endowment for Cancer Research
- Betty Berry Cancer Research Fund
- State of Texas Tobacco Settlement Funds
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 mmunohistochemical 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 nM 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. (C) 2008 Wiley Periodicals, Inc. Head Neck 31: 625-634, 2009
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