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Feiyanning Suppresses Lung Cancer by Targeting Cancer Stem Cell Stemness and NLRP3 Inflammasome

Shuang Wang1, Lifang Wang2, Wan Su2

  • 1Department of Oncology, Shanghai Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

Insights

Feiyanning (FYN) suppresses lung cancer progression by inhibiting the NLRP3 inflammasome and lung cancer stem cells (LCSCs). This Traditional Chinese Medicine shows therapeutic potential by targeting LCSC activation and NLRP3 inflammasome signaling.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Lung cancer stem cells (LCSCs) drive tumor progression and drug resistance.
  • The NLRP3 inflammasome in the inflammatory microenvironment regulates LCSCs.
  • Feiyanning (FYN), a Traditional Chinese Medicine, has potential for lung cancer treatment, but its mechanism is unclear.

Purpose of the Study:

  • To investigate if FYN suppresses lung cancer progression by modulating LCSCs and the NLRP3 inflammasome.
  • To elucidate the underlying mechanisms of FYN's anti-cancer effects.

Main Methods:

  • Established a lung cancer mouse model and treated with FYN and an NLRP3 inhibitor.
  • Sorted and cultured LCSCs (A549 side population cells) using flow cytometry.
  • Assessed proliferation and metastasis using CCK-8 and Transwell assays.
  • Verified effects on stemness markers and NLRP3 inflammasome components via RT-PCR, Western blot, flow cytometry, and immunohistochemistry.

Main Results:

  • FYN suppressed lung cancer cell and LCSC proliferation and metastasis in vitro and in vivo.
  • FYN downregulated key NLRP3 inflammasome components (NLRP3, ASC, caspase-1) and stemness markers (CD44, CD133, Nanog, OCT4, Notch1).
  • NLRP3 knockdown enhanced FYN's inhibitory effects on LCSC metastasis and self-renewal, further suppressing tumor progression.

Conclusions:

  • FYN exerts anti-lung cancer effects by inhibiting NLRP3 activation, thereby suppressing LCSC proliferation and metastasis.
  • FYN targets NLRP3 inflammasome-mediated LCSC activation, revealing a novel link between NLRP3 and LCSCs.
  • Findings suggest FYN as a potential Traditional Chinese Medicine-based therapeutic strategy for lung cancer.

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