Celecoxib disrupts the canonical apoptotic network in HTLV-I cells through activation of Bax and inhibition of PKB/Akt.
Celecoxib disrupts the canonical apoptotic network in HTLV-I cells through activation of Bax and inhibition of PKB/Akt.
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Celecoxib 通过激活 Bax 和抑制 PKB/Akt 来破坏 HTLV-I 细胞中的典型凋亡网络。
DOI：
10.1007/s10495-007-0148-7
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Nicot,Christophe
中科院分区：
文献类型：
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作者：
Sinha-Datta,Uma;Taylor,JohnM;Brown,Megan;Nicot,Christophe
成人t细胞白血病/淋巴瘤（ATLL）是一种侵袭性淋巴细胞增生性疾病，临床预后非常差，与人t细胞白血病病毒I型（HTLV-I）感染有关。由于HTLV-I细胞对大多数诱导凋亡的药物都具有难治性，因此使用常规化疗治疗ATLL患者的益处有限。在这项研究中，我们报道了塞来昔布通过HTLV-I转化白血病细胞的固有线粒体途径诱导细胞死亡。塞来昔布治疗与Bax激活、Mcl-1表达降低、线粒体膜电位丧失和caspase-9依赖性凋亡相关。这些影响与Bcl-2和Bcl-xL无关。我们还发现塞来昔布抑制HTLV-I细胞中Akt/GSK3 β存活通路。
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoproliferative disease of very poor clinical prognosis associated with infection by the human T-cell leukemia virus type I (HTLV-I). Treatment of patients with ATLL using conventional chemotherapy has limited benefit because HTLV-I cells are refractory to most apoptosis-inducing agents. In this study, we report that Celecoxib induces cell death via the intrinsic mitochondrial pathway in HTLV-I transformed leukemia cells. Treatment with Celecoxib was associated with activation of Bax, decreased expression of Mcl-1, loss of the mitochondrial membrane potential and caspase-9-dependent apoptosis. These effects were independent from Bcl-2 and Bcl-xL. We also found that Celecoxib inhibited the Akt/GSK3 β survival pathway in HTLV-I cells.