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[Cancer Research 65, 2899-2905, April 1, 2005]
© 2005 American Association for Cancer Research

Experimental Therapeutics, Molecular Targets, and Chemical Biology

RNA Interference Targeting Aurora Kinase A Suppresses Tumor Growth and Enhances the Taxane Chemosensitivity in Human Pancreatic Cancer Cells

Tatsuo Hata1, Toru Furukawa1, Makoto Sunamura2, Shinichi Egawa2, Fuyuhiko Motoi2, Noriyuki Ohmura2, Tomotoshi Marumoto3, Hideyuki Saya3 and Akira Horii1

Departments of 1 Molecular Pathology and 2 Gastroenterological Surgery, Tohoku University School of Medicine, Sendai Miyagi, Japan and 3 Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

Requests for reprints: Akira Horii, Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. Phone: 81-22-717-8042; Fax: 81-22-717-8047; E-mail: horii{at}mail.tains.tohoku.ac.jp.

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 G2-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.

Key Words: aurora A • pancreatic cancer • RNAi • taxane




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Copyright © 2005 by the American Association for Cancer Research.