Carmustine induces platelet apoptosis
Carmustine induces platelet apoptosis
复制标题
卡莫司汀诱导血小板凋亡
DOI：
10.3109/09537104.2014.928676
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发表时间：
2015-06
期刊：
影响因子：
3.3
通讯作者：
Dai, Kesheng
中科院分区：
文献类型：
--
作者：
Zhang, Yiwen;Zhao, Lili;Yan, Rang;Dai, Kesheng
摘要卡莫司汀是一种烷基化化疗药物，用于治疗脑肿瘤、霍奇金斯、非霍奇金斯淋巴瘤和多发性骨髓瘤等多种恶性肿瘤。但卡莫司汀有血小板减少的副作用，其机制尚不完全清楚。在本研究中，我们发现卡莫司汀剂量依赖性地诱导线粒体内跨膜电位（Δ Δ m）去极化，上调Bax，下调Bcl-2和caspase-3的激活。卡莫司汀不诱导血小板表面P-选择素或PAC-1结合的表达，而明显降低胶原和凝血酶诱导的血小板聚集。Dicumarol，c-Jun NH 2-末端激酶特异性抑制剂，减少卡莫司汀诱导的血小板Δ m去极化。在注射卡莫司汀的小鼠中，循环血小板数量减少，尾部出血时间显著增加。综上所述，这些数据表明卡莫司汀诱导血小板凋亡，提示卡莫司汀治疗患者血小板减少症的可能发病机制。
Abstract Carmustine is one of the alkylating chemotherapeutic agents, which are used to treat various types of cancers, such as brain tumors, Hodgkins and non-Hodgkins lymphoma and multiple myeloma. However, carmustine has the side effect of thrombocytopenia, and the mechanism is not completely understood. In this study, we show that carmustine dose-dependently induced depolarization of mitochondrial inner transmembrane potential (ΔΨm), up-regulation of Bax, down-regulation of Bcl-2 and caspase-3 activation. Carmustine did not induce surface expression of P-selectin or PAC-1 binding, whereas, obviously reduced collagen and thrombin-induced platelet aggregation. Dicumarol, c-Jun NH2-terminal kinase-specific inhibitor, reduced carmustine-induced ΔΨm depolarization in platelets. The numbers of circulating platelets were reduced, and the tail bleeding time was significantly increased in mice that were injected with carmustine. Taken together, these data indicate that carmustine induced platelet apoptosis, suggesting the possible pathogenesis of thrombocytopenia in patients treated with carmustine.
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影响因子：
2.9
作者：
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通讯作者：
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DOI：
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发表时间：
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