Histone acetylation resulting in resistance to methotrexate in choroid plexus cells
Histone acetylation resulting in resistance to methotrexate in choroid plexus cells
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DOI：
10.1007/s11060-008-9709-z
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发表时间：
2009-02-01
影响因子：
3.9
通讯作者：
Wolff, Johannes E. A.
中科院分区：
文献类型：
--
作者：
Prasad, Preethi;Vasquez, Hernan;Wolff, Johannes E. A.
脉络丛癌是一种罕见的肿瘤，通常发生在年幼的儿童。预后很差，并且很少有信息可用于优化治疗方案。我们使用细胞培养模型来评估甲氨蝶呤等化疗药物与丙戊酸和MS-275等组蛋白脱乙酰酶抑制剂（HDACI）联合使用是否可以提高疗效。丙戊酸增加了放射和所有化疗药物在Z310和SV 11小鼠脉络丛细胞系中的细胞毒性，但甲氨蝶呤除外。两种HDACIs都使脉络丛细胞对这种叶酸拮抗剂产生抗性。寻找一个分子的解释，我们发现，胸苷酸合成酶上调时，细胞与HDACI孵育。我们在人脉络丛癌细胞中也证实了这一发现。甲氨蝶呤不应与HDACI联合治疗脉络丛癌。
Choroid plexus carcinomas are rare tumors that typically occur in young children. Prognosis is poor, and very little information is available to optimize treatment protocols. We used a cell culture model to evaluate whether combining chemotherapeutic agents such as methotrexate with histone deacetylase inhibitors (HDACI) such as valproic acid and MS-275 could improve efficacy. Valproic acid increased the cytotoxicity of radiation and of all the chemotherapeutic agents in Z310 and SV11 mouse choroid plexus cell lines, with the exception of methotrexate. Both HDACIs made choroid plexus cells resistant to this folate antagonist. Searching for a molecular explanation, we found that thymidylate synthase was up regulated when the cells were incubated with HDACI. We also confirmed this finding in human choroid plexus carcinoma cells. Methotrexate should not be combined with HDACI in the treatment of choroid plexus carcinoma.