A combination of a DNA-chimera siRNA against PLK-1 and zoledronic acid suppresses the growth of malignant mesothelioma cells in vitro

Kawata, Eri; Ashihara, Eishi; Nakagawa, Yoko; Kiuchi, Takahiro; Ogura, Mai; Yao, Hisayuku; Sakai, Kazuki; Tanaka, Ruriko; Nagao, Rina; Yokota, Asumi; Takeuchi, Miki; Kimura, Shinya; Hirai, Hideyo; Maekawa, Taira

doi:10.1016/j.canlet.2010.02.008

« Previous Next »Cancer Letters
Volume 294, Issue 2 , Pages 245-253, 28 August 2010

A combination of a DNA-chimera siRNA against PLK-1 and zoledronic acid suppresses the growth of malignant mesothelioma cells in vitro

Eri Kawata
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
- Division of Internal Medicine, Kyoto Second Red Cross Hospital, 355 Kamannza Marutamachi, Kamigyo-ku, Kyoto 602-8026, Japan
- These authors contribute equal to this work.
Eishi Ashihara
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
- Corresponding author. Tel.: +81 75 751 3630; fax: +81 75 751 4283.
- These authors contribute equal to this work.
Yoko Nakagawa
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Takahiro Kiuchi
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Mai Ogura
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Hisayuku Yao
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Kazuki Sakai
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Ruriko Tanaka
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Rina Nagao
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Asumi Yokota
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Miki Takeuchi
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Shinya Kimura
- Division of Hematology, Respiratory Medicine, and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
Hideyo Hirai
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
Taira Maekawa
- Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

Received 24 November 2009; received in revised form 6 February 2010; accepted 10 February 2010. published online 08 March 2010.

Abstract

Although novel agents effective against malignant mesothelioma (MM) have been developed, the prognosis of patients with MM is still poor. We generated a DNA-chimeric siRNA against polo-like kinase-1 (PLK-1), which was more stable in human serum than the non-chimeric siRNA. The chimeric PLK-1 siRNA inhibited MM cell proliferation through the induction of apoptosis. Next, we investigated the effects of zoledronic acid (ZOL) on MM cells, and found that ZOL also induced apoptosis in MM cells. Furthermore, ZOL augmented the inhibitory effects of the PLK-1 siRNA. In conclusion, combining a PLK-1 siRNA with ZOL treatment is an attractive strategy against MM.

Keywords: PLK-1, RNA interference, DNA-chimeric siRNA, Bisphosphonate, Malignant mesothelioma