Efficacy of the third-generation bisphosphonate, zoledronic acid alone and combined with anti-cancer agents against small cell lung cancer cell lines

Matsumoto, Seiji; Kimura, Shinya; Segawa, Hidekazu; Kuroda, Junya; Yuasa, Takeshi; Sato, Kiyoshi; Nogawa, Masaki; Tanaka, Fumihiro; Maekawa, Taira; Wada, Hiromi

doi:10.1016/j.lungcan.2004.06.003

« Previous Next »Lung Cancer
Volume 47, Issue 1 , Pages 31-39, January 2005

Efficacy of the third-generation bisphosphonate, zoledronic acid alone and combined with anti-cancer agents against small cell lung cancer cell lines

Seiji Matsumoto
- Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan
Shinya Kimura
- Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan
- Corresponding author. Tel.: +81 75 751 3630; fax: +81 75 751 3631.
Hidekazu Segawa
- Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan
Junya Kuroda
- Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan
Takeshi Yuasa
- Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan
Kiyoshi Sato
- Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan
- Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan
Masaki Nogawa
- Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan
Fumihiro Tanaka
- Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan
Taira Maekawa
- Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan
Hiromi Wada
- Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan

Received 12 January 2004; received in revised form 1 June 2004; accepted 2 June 2004.

Abstract

Small cell lung cancer (SCLC) is one of the most aggressive types of cancers because of its early development of regional and distant metastases. Novel and more effective therapeutic strategies for the treatment of this disease are necessary. Bisphosphonates (BP), originally developed to treat bone disease, have recently been identified as attractive cancer theraptic agents. In this study, we investigated the anti-proliferative effects of zoledronic acid (ZOL) as a single agent and in combination with other agents. ZOL inhibited both farnesylation and geranylgeranylation of RAS related proteins, induced apoptosis and inhibited the growth of eight out of twelve SCLC cell lines examined the in vitro. ZOL also significantly inhibited SCLC tumor growth and SBC-3 cells transplanted subcutaneously into nude mice. Its suppressive effect have not been completed, the addition effect of ZOL with other agents was examined. ZOL augmented the effects of paclitaxel, etoposide, cisplatinum and irinotecan synergistically, and imatinib mesylate additively. These findings indicate that ZOL and combined use of these agents may be promising therapeutic strategies for SCLC.

Keywords: Human, Small cell lung cancer, Bisphosphonate, Zoledronic acid, Imatinib, Anti-cancer agents