Mechanism and therapeutic prospect of resveratrol combined with TRAIL in the treatment of renal cell carcinoma
Mechanism and therapeutic prospect of resveratrol combined with TRAIL in the treatment of renal cell carcinoma
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白藜芦醇联合TRAIL治疗肾细胞癌的机制及治疗前景
DOI：
10.1038/s41417-019-0150-6
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发表时间：
2019-10
期刊：
影响因子：
--
通讯作者：
Na Wei
中科院分区：
文献类型：
--
作者：
Yan Zeng;Feng-di Li;Chun-wei Shi;Jiang-long Du;Yu-Jia Xue;Xin-yuan Liu;Xin Cao;Na Wei
肿瘤坏死因子相关凋亡诱导配体（tumor necrosis factor-related apoptosis-inducing ligand，TRAIL）能杀死多种肿瘤细胞而对正常细胞的作用很小。然而，肾细胞癌（RCC）细胞786-0和OS-RC-2对TRAIL具有抗性。本研究探讨了多酚化合物白藜芦醇（RES）与TRAIL结合的潜力。我们发现RES可以使RCC细胞对TRAIL诱导的死亡敏感。电镜分析表明，RES联合TRAIL可诱导肾癌细胞自噬和凋亡。研究表明，细胞凋亡是caspase依赖性的，caspase-8、caspase-9和caspase-3的激活参与了这一过程。此外，我们还发现，XIAP的表达显着抑制后，RES加TRAIL在RCC细胞。此外，制备了纤维修饰的复制缺陷型腺病毒Ad 5/35-TRAIL，以测试RES和TRAIL在体内的协同作用。我们的数据表明，RES加Ad 5/35-TRAIL显着抑制RCC裸鼠移植瘤生长。这些结果表明，一种新的联合治疗的可能性，导致RCC治疗的改善。
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to kill a wide variety of tumor cells with minimal effects on normal cell. However, renal cell carcinoma (RCC) cells 786-0 and OS-RC-2 were resistant to TRAIL. The present study examines the potential of combining polyphenolic compound resveratrol (RES) with TRAIL. We found that RES can sensitize RCC cells to TRAIL-induced death. Electron microscopy analyses showed that RES plus TRAIL can induce both autophagy and apoptosis in RCC cells. It was proved that the apoptosis is caspase-dependent and the activation of caspase-8, caspase-9, and caspase-3 was involved in this process. Besides, we also found that XIAP expression was significantly inhibited after RES plus TRAIL treatment in RCC cells. Furthermore, a fiber-modified replication-deficient adenovirus Ad5/35-TRAIL was generated to test the synergistic effect of RES and TRAIL in vivo. Our data demonstrated that RES plus Ad5/35-TRAIL significantly inhibited RCC xenograft growth in nude mice. These results suggest the possibility of a new combination therapeutic leading to the improvement of RCC treatment.
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6.1
作者：
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影响因子：
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影响因子：
6.4
作者：
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通讯作者：
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