Co-treatment with arsenic trioxide and ganciclovir reduces tumor volume in a murine xenograft model of nasopharyngeal carcinoma.
Co-treatment with arsenic trioxide and ganciclovir reduces tumor volume in a murine xenograft model of nasopharyngeal carcinoma.
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DOI：
10.1186/1743-422x-10-152
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发表时间：
2013-05-16
期刊：
影响因子：
4.8
通讯作者：
Lasky JA
中科院分区：
文献类型：
--
作者：
Sides MD;Sosulski ML;Luo F;Lin Z;Flemington EK;Lasky JA
我们以前已经表明，早幼粒细胞白血病核小体（PML NB）的破坏足以激活EBV裂解周期，从而使感染的细胞对更昔洛韦（GCV）介导的体外杀伤敏感。在这里，我们表明，共同管理的GCV和三氧化二砷（ATO），一个PML NB破坏剂，减少肿瘤体积在异种移植模型的鼻咽癌利用CNE1细胞。当以药理学水平给药时，GCV和ATO均减少肿瘤生长，而GCV + ATO联合治疗导致肿瘤体积缩小。单独用GCV或ATO处理导致凋亡细胞数量增加，而GCV + ATO协同处理诱导凋亡。用ATO处理或用GCV + ATO共处理导致EBV裂解蛋白的表达。这些数据表明，GCV + ATO联合治疗可能为鼻咽癌患者提供有效的治疗。
We have previously shown that disruption of promyelocytic leukemia nuclear bodies (PML NBs) is sufficient to activate the EBV lytic cycle thus making infected cells susceptible to ganciclovir (GCV) mediated killing in vitro. Here we show that co-administration of GCV and arsenic trioxide (ATO), a PML NB disruptor, reduces tumor volume in a xenograft model of nasopharyngeal carcinoma utilizing CNE1 cells. When administered at pharmacologic levels, both GCV and ATO reduced tumor growth while co-treatment with GCV + ATO resulted in a diminution of tumor volume. Treatment with GCV or ATO individually resulted in an increased number of apoptotic cells while co-treatment with GCV + ATO synergistically induced apoptosis. Treatment with ATO or co-treatment with GCV + ATO resulted in expression of EBV lytic proteins. These data suggest that co-treatment with GCV + ATO may provide an effective treatment for nasopharyngeal carcinoma patients.