Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma.
Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma.
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二氢杨梅素通过 ROS-STAT3 信号促进头颈鳞状细胞癌的自噬和凋亡
DOI：
10.18632/oncotarget.10836
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发表时间：
2016-09-13
期刊：
影响因子：
--
通讯作者：
Zhang WF
中科院分区：
文献类型：
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作者：
Fan TF;Wu TF;Bu LL;Ma SR;Li YC;Mao L;Sun ZJ;Zhang WF
化疗是对抗癌症的有效武器，但许多癌症患者要么对化疗不敏感，要么对目前的化疗方案产生耐药性。因此，迫切需要一种有效的化疗机制，增强肿瘤对化疗药物的敏感性。本研究旨在探讨二氢杨梅素（DHM）对头颈部鳞状细胞癌（HNSCC）的抗肿瘤作用及其机制。我们证明DHM可以显著诱导HNSCC细胞的凋亡性细胞死亡和自噬。同时，增加的自噬抑制细胞凋亡。自噬的药理学或遗传抑制进一步使HNSCC细胞对DHM诱导的细胞凋亡敏感。机制分析表明DHM的抗肿瘤作用可能是通过激活信号转导和转录激活因子3（p-STAT 3）的磷酸化，从而促进自噬。重要的是，DHM触发了HNSCC细胞中活性氧（ROS）的产生，并且ROS的水平随着ROS清除剂N-乙酰半胱氨酸（NAC）而降低。此外，NAC消除了DHM对STAT 3依赖性自噬的影响。总体而言，观察到以下关键问题：首先，DHM通过在头颈部鳞状细胞癌中产生ROS信号通路来增加p-STAT 3依赖性自噬。第二，抑制自噬可增强DHM诱导的头颈部鳞癌细胞凋亡。
Chemotherapy is an effective weapon in the battle against cancer, but numerous cancer patients are either not sensitive to chemotherapy or develop drug resistance to current chemotherapy regimens. Therefore, an effective chemotherapy mechanism that enhances tumor sensitivity to chemotherapeutics is urgently needed. The aim of the present study was to determine the antitumor activity of dihydromyricetin (DHM) on head and neck squamous cell carcinoma (HNSCC) and its underlying mechanisms. We demonstrated that DHM can markedly induce apoptotic cell death and autophagy in HNSCC cells. Meanwhile, increased autophagy inhibited apoptosis. Pharmacological or genetic inhibition of autophagy further sensitized the HNSCC cells to DHM-induced apoptosis. Mechanistic analysis showed that the antitumor of DHM may be due to the activation phosphorylation of signal transducer and activator of transcription 3 (p-STAT3), which contributed to autophagy. Importantly, DHM triggered reactive oxygen species (ROS) generation in the HNSCC cells and the levels of ROS decreased with N-acetyl-cysteine (NAC), a ROS scavenger. Moreover, NAC abrogated the effects of DHM on STAT3-dependent autophagy. Overall, the following critical issues were observed: first, DHM increased the p-STAT3-dependent autophagy by generating ROS-signaling pathways in head and neck squamous cell carcinoma. Second, inhibiting autophagy could enhance DHM-induced apoptosis in head and neck squamous cell carcinoma.