Synergistic anticancer effects of arsenic trioxide with bortezomib in mantle cell lymphoma.
Synergistic anticancer effects of arsenic trioxide with bortezomib in mantle cell lymphoma.
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DOI：
10.1002/ajh.23317
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发表时间：
2012-12
影响因子：
12.8
通讯作者：
McCarty, Nami
中科院分区：
文献类型：
--
作者：
Jung, Hyun Joo;Chen, Zheng;McCarty, Nami
套细胞淋巴瘤 (MCL) 是 B 细胞非霍奇金淋巴瘤 (NHL) 的一种亚型，约占所有淋巴瘤的 6%。 MCL 对大多数化疗（包括基于抗体的新型治疗方法）高度难治，而高级别 MCL 是 NHL 中存活率最差的之一。因此，开发新的治疗策略来克服 MCL 的耐药性非常重要。在本文中，我们测试了三氧化二砷（As2O3，ATO）对硼替佐米耐药的 MCL 的影响。据报道，ATO 可诱导复发性或难治性急性早幼粒细胞白血病患者完全缓解。然而，它们对 MCL 的影响尚未得到探讨。我们在此表明，ATO 通过降低 NF-κB 表达有效抑制 MCL 细胞的生长。 MCL 中细胞凋亡的诱导部分是由于细胞周期蛋白 D1 水平降低和细胞凋亡相关分子水平增加。当细胞同时用ATO处理时，硼替佐米对MCL的抗增殖作用大大增强，表明ATO可以使MCL对硼替佐米敏感。在硼替佐米耐药细胞系中也发现了类似的结果。总之，ATO可能是MCL联合辅助治疗的替代药物，值得进一步的临床试验。
Mantle cell lymphoma (MCL) is a subtype of B-cell Non-Hodgkin’s Lymphoma (NHL) and accounts for approximately 6% of all lymphomas. MCL is highly refractory to most chemotherapy including newer antibody-based therapeutic approaches, and high-grade MCL has one of the worst survival rates among NHLs. Therefore, the development of new therapeutic strategies to overcome drug resistance of MCL is important. In this article, we tested the effects of arsenic trioxide (As2O3, ATO) in bortezomib-resistant MCL. ATO is reported to induce complete remission in the patients with relapsed or refractory acute promyelocytic leukemia. Their effects in MCL, however, have not been explored. We show here that ATO effectively inhibited the growth of MCL cells by reducing NF-κB expression. The induction of apoptosis in MCL was partially due to reduced levels of cyclin D1 and increased levels of apoptosis-related molecules. The antiproliferative effects of bortezomib on MCL greatly increased when the cells were also treated with ATO, indicating ATO can sensitize MCL to bortezomib. Similar results were noted in bortezomib-resistant cell lines. In conclusion, ATO may be an alternative drug for use in combined adjuvant therapies for MCL, and further clinical testing should be performed.
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