Over-expression of Thioredoxin-1 mediates growth, survival, and chemoresistance and is a druggable target in diffuse large B-cell lymphoma.
Over-expression of Thioredoxin-1 mediates growth, survival, and chemoresistance and is a druggable target in diffuse large B-cell lymphoma.
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DOI：
10.18632/oncotarget.463
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Pham LV
中科院分区：
文献类型：
--
作者：
Li C;Thompson MA;Tamayo AT;Zuo Z;Lee J;Vega F;Ford RJ;Pham LV
弥漫性大 B 细胞淋巴瘤 (DLBCL) 是最常见的非霍奇金淋巴瘤，目前最初治疗相当成功，但经常作为难治性疾病复发，导致挽救治疗选择不佳和生存期短。提高 DLBCL 患者生存率的最大挑战是克服化疗耐药性，但其基础尚不清楚。 DLBCL化疗耐药的潜在介质之一是硫氧还蛋白（Trx）家族，主要是因为Trx家族成员在细胞氧化还原稳态的调节中发挥着关键作用，最近的研究表明氧化还原稳态失调也在化疗耐药中发挥着关键作用。在这项研究中，我们发现大多数 DLBCL 衍生细胞系和原代 DLBCL 细胞比正常 B 细胞表达更高的 Trx-1 基础水平，并且 Trx-1 表达水平与患者生存率降低相关。我们的功能研究表明，通过小干扰 RNA 或 Trx-1 抑制剂 (PX-12) 抑制 Trx-1 可抑制 DLBCL 细胞生长和克隆形成，并且还可使 DLBCL 细胞对阿霉素诱导的体外细胞生长抑制敏感。这些结果表明Trx-1在细胞生长和存活以及化疗耐药性中发挥着关键作用，并且是克服复发/难治性DLBCL耐药性的潜在靶点。
Diffuse Large B cell lymphomas (DLBCL) are the most prevalent of the non-Hodgkin lymphomas and are currently initially treated fairly successfully, but frequently relapse as refractory disease, resulting in poor salvage therapy options and short survival. The greatest challenge in improving survival of DLBCL patients is overcoming chemo-resistance, whose basis is poorly understood. Among the potential mediators of DLBCL chemo-resistance is the thioredxoin (Trx) family, primarily because Trx family members play critical roles in the regulation of cellular redox homeostasis, and recent studies have indicated that dysregulated redox homeostasis also plays a key role in chemoresistance. In this study, we showed that most of the DLBCL-derived cell lines and primary DLBCL cells express higher basal levels of Trx-1 than normal B cells and that Trx-1 expression level is associated with decreased patients survival. Our functional studies showed that inhibition of Trx-1 by small interfering RNA or a Trx-1 inhibitor (PX-12) inhibited DLBCL cell growth, clonogenicity, and also sensitized DLBCL cells to doxorubicin-induced cell growth inhibition in vitro. These results indicate that Trx-1 plays a key role in cell growth and survival, as well as chemoresistance, and is a potential target to overcome drug resistance in relapsed/refractory DLBCL.
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影响因子：
2.3
作者：
Efferth, T;Verdorfer, I;Gebhart, E
通讯作者：
Gebhart, E
影响因子：
17.1
作者：
Burington, Bart;Yue, Peng;Dornan, David
通讯作者：
Dornan, David
DOI：
10.1016/j.bbrc.2007.07.033
发表时间：
2007-09-21
影响因子：
3.1
作者：
Chen, Xiao-Ping;Liu, Shou;Chen, Zheng-Wang
通讯作者：
Chen, Zheng-Wang
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
5.7
作者：
Pham LV;Tamayo AT;Li C;Bornmann W;Priebe W;Ford RJ
通讯作者：
Ford RJ