RNA interference targeting aurora kinase A suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells
RNA interference targeting aurora kinase A suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells
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DOI：
10.1158/0008-5472.can-04-3981
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发表时间：
2005-04-01
期刊：
影响因子：
11.2
通讯作者：
Horii, A
中科院分区：
文献类型：
--
作者：
Hata, T;Furukawa, T;Horii, A
AURKA/STK 15/BTAK是编码Aurora A激酶的基因，参与中心体的调节和染色体的分离，在包括胰腺癌在内的各种人类癌症中频繁扩增和过表达。为了探讨其作为胰腺癌治疗靶点的可能性，我们采用RNA干扰技术敲低AURKA表达并分析其表型。我们发现，在培养的胰腺癌细胞中特异性敲低AURKA强烈抑制体外细胞生长和体内致瘤性。敲低诱导细胞在G（2）-M期积聚并最终凋亡。此外，我们观察到的协同增强紫杉烷类，一组化疗药物损害G2-M转换，通过RNA干扰介导的敲低AURKA的细胞毒性。这些结果表明，AURKA表达的抑制可导致人胰腺癌中紫杉烷类的有效抗肿瘤活性和化学增敏活性。
AURKA/STK15/BTAK, the gene encoding Aurora A kinase that is involved in the regulation of centrosomes and segregation of chromosomes, is frequently amplified and overexpressed in various kinds of human cancers, including pancreatic cancer. To address its possibility as a therapeutic target for pancreatic cancer, we employed the RNA interference technique to knockdown AURKA expression and analyzed its phenotypes. We found that the specific knockdown of AURKA in cultured pancreatic cancer cells strongly suppressed in vitro cell growth and in vivo tumorigenicity. The knockdown induced the accumulation of cells in the G(2)-M phase and eventual apoptosis. Furthermore, we observed a synergistic enhancement of the cytotoxicity of taxanes, a group of chemotherapeutic agents impairing G2-M transition, by the RNA interference-mediated knockdown of AURKA. These results indicate that inhibition of AURKA expression can result in potent antitumor activity and chemosensitizing activity to taxanes in human pancreatic cancer.