School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
Oral Oncol. 2009 Dec;45(12):1067-72. doi: 10.1016/j.oraloncology.2009.07.018. Epub 2009 Aug 31.
Esculetin has been shown to selectively induce tumor apoptosis in several types of cancers and is regarded as a promising chemotherapeutic agent. In this study, we showed that esculetin significantly suppressed the growth of oral cancer SAS cells in a dose-dependent manner. DNA content flow cytometry and TUNEL assay revealed that esculetin induced cell cycle arrest and apoptosis. Western blotting showed esculetin increased DR5 protein expression and activated caspase-8, which differed from previous studies conducted in other cell types. Furthermore, treatment with esculetin significantly increased TRAIL-induced apoptosis in SAS cells and the TRAIL-sensitizing effect was blocked by DR5/Fc chimera protein. Our results indicate that esculetin enhances TRAIL-induced apoptosis primarily through upregulation of DR5. Combination of esculetin and TRAIL may be a novel treatment strategy for oral cancers.
七叶灵已被证明能选择性地诱导多种类型癌症的肿瘤细胞凋亡，被认为是一种很有前途的化疗药物。在这项研究中，我们发现七叶灵能显著地抑制口腔癌细胞 SAS 的生长，且呈剂量依赖性。通过 DNA 含量流式细胞术和 TUNEL 检测显示，七叶灵能诱导细胞周期阻滞和细胞凋亡。Western blot 分析表明，七叶灵能增加 DR5 蛋白的表达并激活 caspase-8，这与之前在其他细胞类型中的研究结果不同。此外，七叶灵能显著增加 TRAIL 诱导的 SAS 细胞凋亡，且 DR5/Fc 嵌合蛋白能阻断 TRAIL 的增敏作用。我们的结果表明，七叶灵能通过上调 DR5 增强 TRAIL 诱导的细胞凋亡。七叶灵与 TRAIL 的联合应用可能为口腔癌的治疗提供一种新策略。
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