Adenovirus-mediated gene transfer of caspase-8 sensitizes human adenocarcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand.
Adenovirus-mediated gene transfer of caspase-8 sensitizes human adenocarcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand.
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DOI：
10.3892/ijo.26.2.537
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发表时间：
2005-02
影响因子：
5.2
通讯作者：
H. Yasui;M. Adachi;H. Hamada;K. Imai
中科院分区：
文献类型：
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作者：
H. Yasui;M. Adachi;H. Hamada;K. Imai
对细胞凋亡的抗性与癌细胞对各种抗肿瘤剂的不良反应有关。Caspase-8是与肿瘤坏死因子（TNF）家族死亡受体介导的凋亡信号级联相关的刽子手型caspase家族成员。在这项研究中，具体的caspase-8介导的凋亡活性，我们研究了腺病毒载体表达caspase-8（Adv-caspase-8）与肿瘤坏死因子相关凋亡诱导配体（TRAIL），诱导特异性caspase-8激活的抗肿瘤作用。首先，我们证明了在胰腺癌和结肠癌细胞中，procaspase-8的表达与对TRAIL的凋亡敏感性有关。在人胰腺癌细胞系Panc 1，表现出低表达的procaspase-8，Adv-caspase-8转染强烈增强TRAIL诱导的凋亡。Adv-caspase-8同样增强了人结肠癌细胞系Colo 320 DM对TRAIL的敏感性。这些结果表明，Adv-caspase-8可能是TRAIL的良好组合伴侣，并且使TRAIL在广泛的表现出caspase-8低表达的腺癌细胞中成为更有效的抗癌剂。
Resistance to apoptosis has been implicated in the poor response of cancer cells to various anti-tumor agents. Caspase-8 is a family member of executioner caspases associated with tumor necrosis factor (TNF) family death receptors-mediated apoptotic signaling cascade. In this study, to specify caspase-8-mediated apoptotic activity, we examined the anti-tumor effect of adenoviral vector expressing caspase-8 (Adv-caspase-8) in combination with TNF-related apoptosis-inducing ligand (TRAIL) which induces specifically caspase-8 activation. First, we demonstrated that expression procaspase-8 is related to apoptosis sensitivity to TRAIL in pancreatic and colonic cancer cells. In human pancreatic cancer cell line Panc1 which demonstrates low expression of procaspase-8, Adv-caspase-8 transfection strongly augmented TRAIL-induced apoptosis. Adv-caspase-8 similarly enhanced the susceptibility of human colonic cancer cell line Colo320DM to TRAIL. These results suggest that Adv-caspase-8 may be a good combination partner of TRAIL and enables TRAIL to be a more potent anticancer agent in a wide range of adenocarcinoma cells which demonstrate low expression of caspase-8.