Kit 抑制剂 APcK110 延长 AML 异种移植小鼠模型的生存期。
Kit inhibitor APcK110 extends survival in an AML xenograft mouse model.
机构信息
Department of Leukemia, Unit 428, MD Anderson Cancer Center, The University of Texas, 1515 Holcombe Blvd., Houston, TX 77030, USA.
出版信息
Invest New Drugs. 2011 Oct;29(5):1094-7. doi: 10.1007/s10637-010-9459-6. Epub 2010 Jun 3.
BACKGROUND
Constitutive activation of kit contributes to pathogenesis of acute myeloid leukemia (AML) and targeting Kit may be of therapeutic benefit. APcK110, a novel inhibitor of Kit, has potent proapoptotic and antiproliferative activity in AML cell lines and primary AML samples. Here we extend our studies to the activity of APcK110 in a xenograft mouse model.
METHODS
After sub-lethal whole body radiation, OCI/AML3 cells were injected intravenously in NOD-SCID mice. Ten days later, either APcK110 or phosphate buffered saline (PBS) was injected intraperitoneally every other day. Kaplan-Meier estimates were used to calculate survival.
RESULTS
We show that 1) all mice injected with OCI/AML3 cells developed a clinical and histological picture consistent with myelomonocytic AML; and 2) survival of APcK110-treated mice was significantly longer compared with mice injected with PBS (p = .02).
CONCLUSIONS
APcK110 is a novel kit kinase inhibitor with anti-AML activity in vitro and in vivo. Further evaluation in toxicology and clinical studies is warranted.
背景
Kit 的组成性激活有助于急性髓系白血病（AML）的发病机制，靶向 Kit 可能具有治疗益处。APcK110 是一种新型的 Kit 抑制剂，在 AML 细胞系和原发性 AML 样本中具有很强的促凋亡和抗增殖活性。在这里，我们将研究扩展到 APcK110 在异种移植小鼠模型中的活性。
方法
在亚致死全身辐射后，将 OCI/AML3 细胞静脉注射到 NOD-SCID 小鼠中。 10 天后，每隔一天腹膜内注射 APcK110 或磷酸盐缓冲盐水（PBS）。使用 Kaplan-Meier 估计来计算存活率。
结果
我们表明：1）所有注射 OCI/AML3 细胞的小鼠均出现与髓单核细胞性 AML 一致的临床和组织学表现；2）与注射 PBS 的小鼠相比，APcK110 治疗的小鼠的存活率显著延长（p =.02）。
结论
APcK110 是一种新型的 Kit 激酶抑制剂，具有体外和体内抗 AML 活性。需要进一步在毒理学和临床研究中进行评估。
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