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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.
Introduction:
Lung cancer stem cells (LCSCs) are closely linked to lung cancer progression and drug resistance, and are regulated by the inflammatory microenvironment, such as NLR family pyrin domain containing 3 (NLRP3) inflammasome. Feiyanning (FYN) is a Traditional Chinese Medicine with therapeutic potential for lung cancer. However, its mechanism remains elusive. This study aimed to investigate whether FYN suppresses lung cancer progression by modulating LCSCs and the NLRP3 inflammasome.
Methods:
A A549 tumor-bearing mouse model was established, and FYN and an NLRP3 inhibitor were administered to evaluate their anti-lung cancer efficacy. A549 side population (SP) stem cells as LCSCs were sorted by flow cytometry and cultured. The effects of FYN on the proliferation and metastasis of A549 cells and LCSCs were evaluated by CCK-8 and Transwell assays. The effects of FYN on the stemness of LCSCs and inflammasome NLRP3 in A549 cells and tumor tissues were verified by RT-PCR, Western blot, flow cytometry, and immunohistochemistry.
Results:
In vitro and in vivo experiments demonstrated that FYN suppressed lung cancer cell proliferation and metastasis while downregulating key NLRP3 inflammasome components (NLRP3, ASC, caspase-1). FYN inhibited the proliferation and metastasis of LCSCs sorted by flow cytometry. Western Blot analysis revealed consistent downregulation of stem cell markers (CD44 and CD133) and stem cell stemness markers (Nanog, OCT4, and Notch1) in FYN-treated LCSCs. Notably, NLRP3 knockdown further enhanced the inhibitory effects of FYN on the metastasis and self-renewal ability of LCSCs, thereby further suppressing the progression of lung cancer.
Discussion:
FYN exerted anti-lung cancer effects by suppressing the proliferation and metastasis of lung cancer cells and LCSCs both in vitro and in vivo by inhibiting NLRP3 activation.
Conclusion:
Our findings demonstrated that FYN exerts its anti-tumor effects by targeting NLRP3 inflammasome- mediated LCSC activation and identified a novel link between the NLRP3 inflammasome and LCSCs. The results also provided novel mechanistic insights and a potential TCM-based therapeutic strategy for lung cancer intervention.
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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