(-)-Guaiol regulates RAD51 stability via autophagy to induce cell apoptosis in non-small cell lung cancer.
(-)-Guaiol regulates RAD51 stability via autophagy to induce cell apoptosis in non-small cell lung cancer.
复制标题
(-)-愈创木酚通过自噬调节 RAD51 稳定性诱导非小细胞肺癌细胞凋亡
DOI：
10.18632/oncotarget.11540
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发表时间：
2016-09-20
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
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作者：
Yang Q;Wu J;Luo Y;Huang N;Zhen N;Zhou Y;Sun F;Li Z;Pan Q;Li Y
（−）-愈创酚，通常被认为是一种抗菌化合物，已经在许多药用植物中发现。其在肿瘤抑制中的作用仍在研究中。在本研究中，我们主要探讨其在治疗非小细胞肺癌（NSCLC）中的应用及其机制。在这里，我们发现(−)-愈创木酚在体外和体内都能显著抑制非小细胞肺癌细胞的生长。进一步的高通量分析表明，同源重组修复的关键因子RAD51是它的潜在靶点。以下机制研究表明(−)-愈创酚参与细胞自噬调节RAD51的表达，导致双链断裂引发细胞凋亡。此外，靶向在肺腺癌组织中高度过表达的RAD51，在体外和体内均可显著提高NSCLC细胞对(−)-愈创酚的化疗敏感性。总之，我们的研究为将(−)-愈创木酚应用于NSCLC治疗提供了有吸引力的见解，并进一步表明，敲低致癌RAD51将大大提高NSCLC患者的化疗敏感性。
(−)-Guaiol, generally known as an antibacterial compound, has been found in many medicinal plants. Its roles in tumor suppression are still under investigation. In the study, we mainly focused on exploring its applications in dealing with non-small cell lung cancer (NSCLC) and the underlying mechanisms. Here, we show that (−)-Guaiol significantly inhibits cell growth of NSCLC cells both in vitro and in vivo. Further high throughput analysis reveals that RAD51, a pivotal factor in homologous recombination repair, is a potential target for it. The following mechanism studies show that (−)-Guaiol is involved in cell autophagy to regulate the expression of RAD51, leading to double-strand breaks triggered cell apoptosis. Moreover, targeting RAD51, which is highly overexpressed in the lung adenocarcinoma tissues, can significantly increase the chemosensitivity of NSCLC cells to (−)-Guaiol both in vitro and in vivo. All in all, our studies provide an attractive insight in applying (−)-Guaiol into NSCLC treatments and further suggest that knockdown of oncogenic RAD51 will greatly enhance the chemosensitivity of patients with NSCLC.