OncoTargets and Therapy (Sep 2020)

Mechanism of Sanguinarine in Inhibiting Macrophages to Promote Metastasis and Proliferation of Lung Cancer via Modulating the Exosomes in A549 Cells

  • Yu Y,
  • Luo Y,
  • Fang Z,
  • Teng W,
  • Yu Y,
  • Tian J,
  • Guo P,
  • Xu R,
  • Wu J,
  • Li Y

Journal volume & issue
Vol. Volume 13
pp. 8989 – 9003

Abstract

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Yuanyuan Yu,1,* Yingbin Luo,1,* Zhihong Fang,1 Wenjing Teng,1 Yongchun Yu,2 Jianhui Tian,3 Peng Guo,1 Rongzhong Xu,1 Jianchun Wu,1 Yan Li1 1Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, People’s Republic of China; 2Institute for Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China; 3Institute of Traditional Chinese Medicine in Oncology, Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Li; Jianchun WuDepartment of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, No. 274, Zhijiang Road, Jing’an District, Shanghai 200071, People’s Republic of ChinaTel/Fax +86-21-63925588Email [email protected]; [email protected]: Sanguinarine (SNG) is a benzophenanthridine alkaloid obtained from the roots of Sanguinaria canadensis and has an anticancer effect. The aim of this study was to explore the mechanism of SNG in inhibiting macrophages via regulating the exosomes derived from lung carcinoma cells to reduce metastasis and proliferation of lung carcinoma.Methods: Human lung cancer cells (A549 cells) were treated with 4μM of SNG. Exosomes of A549 cells were extracted from A549 cells supernatant, and THP-1 cells were cultured with exosomes. Then, the supernatant of THP-1 cells was collected and cultured with A549 cells. Cell proliferation was measured via plate clone formation and CCK-8 assays. Migration was assessed by using Transwell assay and scratch test. Cellular invasion was detected by Transwell assay. Apoptosis was determined using flow cytometry. Moreover, the protein expressions of GAPDH, P65 and P-P65 in THP-1 cells were measured by Western blot. Levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and chemotactic cytokines ligand 2 (CCL-2) extracted from THP-1 cells were determined by reverse transcription-polymerase chain reaction (RT-PCR).Results: Compared to the control group, exosomes could activate THP-1 cells, and the invasion, migration, and proliferation of A549 cells were consequently enhanced. Exosomes could increase the protein expression of p-p65 and the RNA expression levels of TNF-α, IL-6, and CCL-2 in THP-1 cells. Compared with the exosome group, SNG-treated exosomes inhibited THP-1 cells so that the invasion, proliferation, and migration of A549 cells were attenuated and apoptosis was promoted. In THP-1 cells, SNG-treated exosomes inhibited P-P65 expression and the RNA expression levels of TNF-α, IL-6, and CCL-2.Conclusion: Exosomes treated by SNG inhibited THP-1 cells so that the invasion, proliferation, and migration of A549 cells were inhibited, and the apoptosis was promoted. The mechanism is possibly associated with the inhibition of NF-κB pathway in THP-1 cells.Keywords: SNG, exosomes, THP-1 cells, NF-κB signaling pathway

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