Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway.
Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway.
复制标题
水飞蓟宾通过靶向 EGFR/LOX 通路抑制 NSCLC 转移
DOI：
10.3389/fphar.2018.00021
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发表时间：
2018
影响因子：
5.6
通讯作者：
Sun L
中科院分区：
文献类型：
--
作者：
Hou X;Du H;Quan X;Shi L;Zhang Q;Wu Y;Liu Y;Xiao J;Li Y;Lu L;Ai X;Zhan M;Yuan S;Sun L
肿瘤转移是威胁癌症患者的最致命和使人衰弱的过程。在参与肿瘤转移的调节剂中，赖氨酰氧化酶（LOX）是肿瘤侵袭、迁移和转移前小生境形成的重要贡献者。虽然LOX与肺部患者预后不良的关系已有初步报道，但其机制仍不清楚。在此，我们发现LOX过表达与肺腺癌患者的生存密切相关，而与肺鳞癌患者的生存无关。此外，我们证实，LOX的表达是通过激活表皮生长因子受体（EGFR）通过PI 3 K/AKT，MEK/ERK，和SAPK/JNK信号通路在非小细胞肺癌（NSCLC）的调节。同时，本研究也提示传统抗纤维化药物水飞蓟宾以EGFR/LOX依赖的方式抑制NSCLC细胞迁移。此外，原位种植转移模型也证实了EGFR抑制剂WZ 4002和水飞蓟宾通过EGFR/LOX途径减少肿瘤转移。总之，本研究揭示LOX表达受EGFR途径调节，这可能解释水飞蓟宾的抗癌转移作用，表明LOX是NSCLC治疗的潜在治疗靶点。
Tumor metastasis is the most lethal and debilitating process that threatens cancer patients. Among the regulators involved in tumor metastasis, lysyl oxidase (LOX) is an important contributor for tumor invasion, migration and the formation of the pre-metastatic niche. Although the relationship between LOX and poor prognosis of lung patients has been preliminary reported, the mechanism remains poorly understood. Here, we found that LOX overexpression is closely related to the survival of lung adenocarcinoma patients but not squamous cell carcinoma patients. Moreover, we confirmed that LOX expression is regulated by the activation of epidermal growth factor receptor (EGFR) via the PI3K/AKT, MEK/ERK, and SAPK/JNK signaling pathways in non-small cell lung cancer (NSCLC). Meanwhile, the study also suggested that the traditional anti-fibrosis drug silibinin inhibited NSCLC cell migration in an EGFR/LOX dependent manner. In addition, an orthotopic implantation metastasis model also confirmed that the EGFR inhibitor WZ4002 and silibinin decreased tumor metastasis through the EGFR/LOX pathway. Altogether, this study revealed that LOX expression is regulated by the EGFR pathway and this may account for the anti-cancer metastasis effects of silibinin, indicating LOX as a potentially therapeutic target for NSCLC treatment.