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  2. Corylin inhibits the progression of Non-small cell lung cancer cells by regulating NF-κB signaling pathway via targeting p65

Corylin inhibits the progression of Non-small cell lung cancer cells by regulating NF-κB signaling pathway via targeting p65

  • Phytomedicine. 2023 Feb:110:154627. doi: 10.1016/j.phymed.2022.154627.
Zihan Lin 1 Lijuan Liao 2 Shengchao Zhao 3 Wei Gu 1 Guanzhen Wang 3 Ziyi Shen 1 Yuanhui Wang 1 Kun Chen 1 Wei Liu 4 Yi Cai 5 Chunpeng Wan 6 Tingdong Yan 7
Affiliations

Affiliations

  • 1 School of Life Sciences, Shanghai University, Shanghai 200444, China.
  • 2 Department of Pathology, Women and Children's Hospital, Decheng Dezhou, Shandong 253017, China.
  • 3 School of Life Sciences, Shanghai University, Shanghai 200444, China; Key Lab of Natural Product Chemistry and Application at Universities of Education Department of Xinjiang Uygur Autonomous Region, Yili Normal University, Yining 835000, China.
  • 4 Key Lab of Natural Product Chemistry and Application at Universities of Education Department of Xinjiang Uygur Autonomous Region, Yili Normal University, Yining 835000, China.
  • 5 Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China. Electronic address: [email protected].
  • 6 Jiangxi Key Laboratory for Postharvest Technology and Nondestructive Testing of Fruits & Vegetables, College of Agronomy, Jiangxi Agricultural University, Nanchang 330045, China. Electronic address: [email protected].
  • 7 School of Life Sciences, Shanghai University, Shanghai 200444, China; Zhejiang Xinda Hospital, Huzhou 313099, China. Electronic address: [email protected].
Abstract

Background: Lung Cancer is characterized by high-risk and high mortality, among which non-small cell lung Cancer (NSCLC) conquers a dominant position. Previous studies have reported that corylin has anti-inflammatory, anti-oxidant, and anti-tumor effects; however, its role in NSCLC cells remains unclear.

Hypothesis: Corylin inhibits the progression of NSCLC cells.

Methods: A lentivector NF-κB luciferase reporter was constructed by molecular cloning. Corylin was screened and identified as an NF-κB pathway inhibitor by luciferase reporter assay. Corylin inhibited the expression of NF-κB downstream genes, which was detected by qRT-PCR. The effect of corylin on NSCLC cells was detected by colony formation assay, cell Apoptosis, cell proliferation, in vitro invasion, and cell scratch assay. Corylin inhibited p65 nuclear translocation and was detected by molecular docking, immunofluorescence assay, and Western blot analysis.

Results: We constructed a lentiviral expression vector, containing an NF-κB luciferase reporter and established a stable A549 cell line for its expression. Using this cell line, corylin was screened and identified as an NF-κB pathway inhibitor. It was found that corylin inhibited the expression of NF-κB downstream genes and inhibited the proliferation and migration of NSCLC cells. Meanwhile, it was also found that corylin significantly reversed the increased proliferation of NSCLC cell lines induced by p65 overexpression. Molecular docking analysis showed that corylin could bind to p65 by hydrogen bonding. Further study showed that corylin inhibited the NF-κB signaling pathway by blocking p65 nuclear translocation.

Conclusions: Our study screened and identified corylin as an NF-κB Inhibitor and elucidated the molecular mechanism by which corylin inhibits the growth of NSCLC cells. The present study provides a novel strategy for improving the prognosis and treatment of NSCLC patients.

Keywords

Corylin; NF-κB; Natural products; Non-small cell lung cancer; p65.

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