Aurora kinase A inhibition and paclitaxel as targeted combination therapy for head and neck squamous cell carcinoma.
Aurora kinase A inhibition and paclitaxel as targeted combination therapy for head and neck squamous cell carcinoma.
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Aurora激酶A抑制作用和紫杉醇作为头颈鳞状细胞癌的靶向组合疗法。
DOI：
10.1002/hed.21007
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发表时间：
2009-05
影响因子：
2.9
通讯作者：
Clayman, Gary L.
中科院分区：
文献类型：
--
作者：
Mazumdar, Abhijit;Henderson, Ying C.;El-Naggar, Adel K.;Sen, Subrata;Clayman, Gary L.
极光激酶A（AURKA）在多种人类癌症（包括头颈部鳞状细胞癌（HNSCC））中以不同的发生率扩增。我们研究了AURKA是否是HNSCC的潜在治疗靶点。我们对配对的正常和肿瘤样本（n = 63）中的AURKA表达进行了免疫组织化学分析。通过RT-PCR和蛋白质印迹分析评估用AURKA特异性siRNA处理的HNSCC细胞的AURKA mRNA和蛋白质表达水平。通过MTT测定评估用siRNA和紫杉醇处理的肿瘤细胞的细胞增殖，并通过流式细胞术评估细胞周期分布。在大多数（85%）分析的样本中，AURKA在肿瘤中的表达高于邻近正常组织。HNSCC细胞和原发性肿瘤显示AURKA的高表达水平。大多数原发性肿瘤也表现出高激酶活性的酶。靶向AURKA抑制增加了亚G1细胞分数，伴随着G1细胞群的减少，表明诱导了细胞凋亡，从而显著抑制了HNSCC细胞的增殖。将siRNA诱导的AURKA抑制与5-10 nM紫杉醇组合协同增强凋亡诱导。AURKA是HNSCC潜在的治疗靶点。需要进一步研究小分子AURKA抑制剂作为治疗剂。
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. 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 RT-PCR 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. 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 5-10 nM paclitaxel synergistically enhanced apoptosis induction. AURKA is a potential therapeutic target for HNSCC. Further investigation of small-molecule AURKA inhibitors as therapeutic agents is warranted.
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影响因子：
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