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Hou X, Du H, Quan X, et al. Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway. Front Pharmacol. 2018;9:21doi: 10.3389/fphar.2018.00021.
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. (2018). Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway. Frontiers in pharmacology, 921. https://doi.org/10.3389/fphar.2018.00021
Hou, Xiaoying, et al. "Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway." Frontiers in pharmacology vol. 9 (2018): 21. doi: https://doi.org/10.3389/fphar.2018.00021
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. Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway. Front Pharmacol. 2018 Feb 08;9:21. doi: 10.3389/fphar.2018.00021. eCollection 2018. PMID: 29472856; PMCID: PMC5809401.
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Front Pharmacol. 2018 Feb 08;9:21. doi: 10.3389/fphar.2018.00021. eCollection 2018.

Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway.

Frontiers in pharmacology

Xiaoying Hou, Hongzhi Du, Xingping Quan, Lei Shi, Qianqian Zhang, Yao Wu, Yang Liu, Jing Xiao, Yong Li, Ligong Lu, Xun Ai, Meixiao Zhan, Shengtao Yuan, Li Sun

Affiliations

  1. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.
  2. Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, China.
  3. Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, China.
  4. School of Pharmaceutical, Lanzhou University, Lanzhou, China.
  5. Center of Intervention Radiology, Zhuhai Precision Medicine Center, Zhuhai People's Hospital, Zhuhai, China.
  6. Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, IL, United States.

PMID: 29472856 PMCID: PMC5809401 DOI: 10.3389/fphar.2018.00021

Abstract

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.

Keywords: EGFR; NSCLC; lysyl oxidase; metastasis; silibinin

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