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

被引:121
作者
Matsumoto, S
Kimura, S
Segawa, H
Kuroda, J
Yuasa, T
Sato, K
Nogawa, M
Tanaka, F
Maekawa, T
Wada, H
机构
[1] Kyoto Univ Hosp, Dept Transfus Med & Cell Therapy, Sakyo Ku, Kyoto 6068507, Japan
[2] Kyoto Univ, Fac Med, Dept Thorac Surg, Kyoto 6068507, Japan
关键词
human; small cell lung cancer; bisphosphonate; zoledronic acid; imatinib; anti-cancer agents;
D O I
10.1016/j.lungcan.2004.06.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 am 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. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:31 / 39
页数:9
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