1. Academic Validation
  2. Schizandrin A enhances the efficacy of gefitinib by suppressing IKKβ/NF-κB signaling in non-small cell lung cancer

Schizandrin A enhances the efficacy of gefitinib by suppressing IKKβ/NF-κB signaling in non-small cell lung cancer

  • Eur J Pharmacol. 2019 Jul 15;855:10-19. doi: 10.1016/j.ejphar.2019.04.016.
Haibing Xian 1 Weineng Feng 2 Jiren Zhang 3
Affiliations

Affiliations

  • 1 Department of Oncology, Zhujiang Hospital, Southern Medical University/The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510282, Guangdong, China; Department of Head and Neck/Thoracic Medical Oncology, The First People's Hospital of Foshan, Foshan, 528041, Guangdong, China.
  • 2 Department of Head and Neck/Thoracic Medical Oncology, The First People's Hospital of Foshan, Foshan, 528041, Guangdong, China.
  • 3 Department of Oncology, Zhujiang Hospital, Southern Medical University/The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510282, Guangdong, China. Electronic address: zhangjiren2015@163.com.
Abstract

The emergence of resistance to EGF receptor (EGFR) inhibitor therapy is a significant challenge for patients with non-small cell lung Cancer (NSCLC). During the past few years, a correlation between EGFR TKIs resistance and dysregulation of IKKβ/NF-κB signaling has been increasingly suggested. However, few studies have focused on the effects of combining IKK/NF-κB and EGFR inhibitors to overcome EGFR TKIs resistance. In this study, we discovered that Schizandrin A (Sch A), a lignin compound isolated from Schisandra chinesnesis, could synergize with the EGFR receptor inhibitor Gefitinib to inhibit cell growth, induce cell cycle arrest and Apoptosis of HCC827/GR cells. Sch A effectively suppressed the phosphorylation of IKKβ and IκBα, as well as the nuclear translocation of NF-κB p65, and showed high and selective affinity for IKKβ in surface plasmon resonance (SPR) experiments, indicating that Sch A was a selective IKKβ inhibitor. Molecular modeling between IKKβ and Sch A suggested that Sch A formed key hydrophobic interactions with IKKβ, which may contribute to its potent IKKβ inhibitory effect. These findings suggest a novel approach to improve poor clinical outcomes in EGFR TKIs therapy, by combining it with Sch A.

Keywords

Gefitinib; IKKβ/NF-κB signal; NSCLC; Schizandrin A.

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