Inostamycin enhanced TRAIL-induced apoptosis through DR5 upregulation on the cell surface
Inostamycin enhanced TRAIL-induced apoptosis through DR5 upregulation on the cell surface
复制标题
肌霉素通过细胞表面 DR5 上调增强 TRAIL 诱导的细胞凋亡
DOI：
10.1038/ja.2012.21
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
M. Imoto
中科院分区：
文献类型：
--
作者：
Kohta Yamamoto;Masafumi Makino;R. Watanapokasin;E. Tashiro;M. Imoto
肿瘤坏死因子相关凋亡诱导配体（Tumor necrosis factor-related apoptosis-inducing ligand， TRAIL）已被认为是一种可能的治疗癌症的药物。这是因为它对各种癌细胞具有选择性的细胞毒性，而对正常细胞没有有害影响。然而，最近的研究报道，TRAIL在癌症治疗中的潜在应用是有限的，因为许多癌细胞已被发现对TRAIL有耐药性。因此，增强TRAIL细胞毒性的小分子化合物将是与TRAIL联合治疗应用的战略候选者。本研究发现，inostamycin和TRAIL联合治疗可协同诱导HCT116细胞caspase依赖性凋亡。肌stamycin上调DR5，而DR5的下调抑制了肌stamycin和TRAIL共同诱导的细胞凋亡。此外，肌stamycin增加了细胞表面DR5的表达。因此，inostamycin增加的细胞表面DR5表达可能促进了trail诱导的细胞凋亡。我们的研究表明，inostamycin和TRAIL联合治疗可能提供了一种克服肿瘤细胞中TRAIL耐药的策略。
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been considered as a possible therapeutic agent for cancer treatment. This is because of its selective cytotoxicity against various cancer cells without a detrimental effect on normal cells. However, recent studies have reported that the potential application of TRAIL in cancer therapy is limited, as many cancer cells have been found to be resistant to TRAIL. Therefore, small molecule compounds that potentiate the cytotoxicity of TRAIL would be strategic candidates for therapeutic applications in combination with TRAIL. Here we found that a combined treatment of inostamycin and TRAIL synergistically induced caspase-dependent apoptosis in HCT116 cells. Inostamycin upregulated DR5, and a knockdown of DR5 suppressed the apoptosis that was synergistically induced by co-treatment with inostamycin and TRAIL. Moreover, inostamycin increased the expression of DR5 on the cell surface. Therefore, inostamycin-increased cell surface expression of DR5 may have contributed to the enhancement of TRAIL-induced apoptosis. Our study suggests that combined treatment with inostamycin and TRAIL may offer a strategy to overcome TRAIL resistance in tumor cells.
影响因子：
32.4
作者：
Wiley, SR;Schooley, K;Goodwin, RG
通讯作者：
Goodwin, RG