Kimura Shinya, Kuroda Junya, Segawa Hidekazu, Sato Kiyoshi, Nogawa Masaki, Yuasa Takeshi, Ottmann Oliver G, Maekawa Taira
Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
Int J Hematol. 2004 Jan;79(1):37-43. doi: 10.1007/BF02983531.
Bisphosphonates are widely used to treat bone diseases and appear to possess antitumor activity. Moreover, we recently found that a third-generation bisphosphonate, zoledronic acid (ZOL), synergistically interacts with imatinib in vitro and in vivo to induce antileukemic activity, and others have reported that ZOL interacts synergistically with paclitaxel. Thus, the efficacy of other antileukemic agents combined with ZOL should be evaluated experimentally. In this study, we investigated the effects of concurrent and sequential combinations of ZOL with several commonly used antileukemic agents, including imatinib, on the in vitro growth of leukemia cell lines. As a complement to our previous finding that ZOL synergistically augments the effects of imatinib, we report here that ZOL acts additively when administered concurrently with hydroxyurea (HU), cytarabine (Ara-C), or daunorubicin (DNR) in some leukemic cell lines. Furthermore, one day of ZOL pretreatment augmented the sensitivity of imatinib and Ara-C. Therefore, concurrent or sequential administration of ZOL with imatinib, HU, Ara-C, or DNR may increase the efficacy of leukemia treatment.
双膦酸盐被广泛用于治疗骨骼疾病，并且似乎具有抗肿瘤活性。此外，我们最近发现，第三代双膦酸盐唑来膦酸（ZOL）在体外和体内与伊马替尼协同相互作用以诱导抗白血病活性，并且其他人报道ZOL与紫杉醇协同相互作用。因此，其他抗白血病药物与ZOL联合使用的疗效应通过实验进行评估。在本研究中，我们研究了ZOL与几种常用抗白血病药物（包括伊马替尼）同时和序贯联合对白血病细胞系体外生长的影响。作为对我们之前发现ZOL协同增强伊马替尼作用的补充，我们在此报告，在一些白血病细胞系中，ZOL与羟基脲（HU）、阿糖胞苷（Ara-C）或柔红霉素（DNR）同时给药时具有相加作用。此外，一天的ZOL预处理增强了伊马替尼和Ara-C的敏感性。因此，ZOL与伊马替尼、HU、Ara-C或DNR同时或序贯给药可能会提高白血病治疗的疗效。
