Department of Oncology, Harbin Medical University, Harbin, People's Republic of China.
Neoplasma. 2012;59(1):18-29. doi: 10.4149/neo_2012_003.
The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in tumor cells. But studies have demonstrated that many tumor cells were resistant to TRAIL-induced apoptosis. CYLD is recognized as a negative regulator of nuclear factor-kappa B(NF-κB) activity. To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF-κB activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF-κB activity.
死亡配体肿瘤坏死因子相关凋亡诱导配体（TRAIL）可以选择性地诱导肿瘤细胞凋亡。但是研究表明，许多肿瘤细胞对 TRAIL 诱导的凋亡具有抗性。CYLD 被认为是核因子-κB（NF-κB）活性的负调节剂。为了探讨 CYLD 表达与肺癌细胞系对 TRAIL 反应性之间的相关性，我们建立了稳定表达 CYLD 的肺癌细胞系。我们的数据首次提供了证据表明，CYLD 的表达增加直接阻断 TRAIL 诱导的 NF-κB 激活，从而增加肺癌细胞中 TRAIL 诱导的凋亡。CYLD 可能作为肺癌的治疗靶点。针对 CYLD 与 TRAIL 的联合治疗可能是一种治疗 NF-κB 活性高的肺癌的新策略。
