Ibuprofen enhances TRAIL-induced apoptosis through DR5 upregulation.
Ibuprofen enhances TRAIL-induced apoptosis through DR5 upregulation.
复制标题
DOI：
10.3892/or.2013.2713
复制
发表时间：
2013-11
期刊：
影响因子：
4.2
通讯作者：
Momoko Todo;Mano Horinaka;Mitsuhiro Tomosugi;R. Tanaka;Haruna Ikawa;Y. Sowa;H. Ishikawa;H. Fujiwara-H.-Fuj
中科院分区：
文献类型：
--
作者：
Momoko Todo;Mano Horinaka;Mitsuhiro Tomosugi;R. Tanaka;Haruna Ikawa;Y. Sowa;H. Ishikawa;H. Fujiwara-H.-Fuj
大量的人类化学预防研究表明，非甾体抗炎药（NSAIDs）对多种恶性肿瘤具有化学预防作用。然而，已经有许多关于阿司匹林的临床研究，而不是布洛芬，尽管布洛芬是临床上最安全使用的NSAID之一，显示出有效的抗炎作用。此外，我们报道了许多化学预防剂增强肿瘤坏死因子相关凋亡诱导配体（TRAIL）的凋亡诱导作用，这是已知的癌症预防的关键。因此，我们研究了布洛芬是否增强了TRAIL的杀细胞作用，并发现布洛芬显著刺激了TRAIL对人结肠癌HCT 116细胞的凋亡诱导功效。通过Western印迹分析和实时RT-PCR检测，布洛芬上调死亡受体5（DR 5），TRAIL受体的表达。TRAIL诱导的细胞凋亡增强布洛芬有效地减少了半胱天冬酶抑制剂和显性负DR 5。值得注意的是，布洛芬与TRAIL的共同治疗没有增强正常外周血单核细胞（PBMC）的凋亡。这些结果表明，布洛芬和TRAIL协同诱导人结肠癌HCT 116细胞的凋亡，而不是在正常的PBMC中，提高了布洛芬可能是有前途的安全的化学预防剂对结肠癌的可能性。
Numerous human chemoprevention studies have demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs) possess chemopreventive effects against a variety of malignant tumors. However, there have been many clinical studies on aspirin, but not ibuprofen, even though ibuprofen is one of the most clinically and safely used NSAIDs showing potent anti-inflammatory effects. Moreover, we reported that many chemopreventive agents enhance the apoptosis-inducing effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is known to be crucial for cancer prevention. We, therefore, investigated whether ibuprofen enhances the cytocidal effect of TRAIL and found that ibuprofen markedly stimulated the apoptosis-inducing efficacy of TRAIL against human colon cancer HCT116 cells. As detected by western blot analysis and real-time RT-PCR, ibuprofen upregulated the expression of death receptor 5 (DR5), a TRAIL receptor. TRAIL-induced apoptosis enhanced by ibuprofen was effectively decreased by a caspase inhibitor and dominant-negative DR5. Noteworthy, co-treatment of ibuprofen with TRAIL did not enhance apoptosis in normal peripheral blood mononuclear cells (PBMCs). These results demonstrated that ibuprofen and TRAIL synergistically induced apoptosis in human colon cancer HCT116 cells but not in normal PBMCs, raising the possibility that ibuprofen may be promising as a safe chemopreventive agent against colon cancer.