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Published on: October 10, 2025
Diosgenin Attenuates Angiogenesis via Targeting Src/STAT3 Signaling Pathway to Treat Non-Small Cell Lung Cancer
Wan-Yu Li1, Yu-Han Wang1, Qing-Ting Wang1
1Department of Integrated Traditional Chinese and Western Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
Objective:
To investigate the anti-tumor and anti-angiogenic effects of diosgenin (Dio) in lung cancer.
Methods:
Effect of Dio (0-50 µmol/L) on apoptosis and proliferation in non-small cell lung cancer (NSCLC) cells A549 and H1299 were evaluated by flow cytometry and colony formation assays. Transwell and angiogenesis experiments were used to assess Dio's impact on vascular formation and migration of human wmbilical vein endothelial cells. Network pharmacology and molecular docking were combined to explore Dio's anti-lung cancer mechanisms. Dio's influence on Src/STAT3 pathway and angiogenic factors were evaluated by Western blot. C57BL/6 mice implanted with LLC cells and BALB/c-nu nude mice implanted with A549 cells (n=10 each group) were continuously treated with Dio (20 mg/kg) or solvent for 21 d to valid the anti-tumor efficacy of Dio.
Results:
Dio effectively inhibited the growth of NSCLC cells in vitro and suppressed tumor angiogenesis (P<0.01). Further network pharmacology analysis identified relevant pathways, and in vitro experiments confirmed that Dio exerted its anti-tumor effects and anti-angiogenic properties through Src/STAT3 pathway. It inhibits the synthesis and secretion of angiogenic factors vascular endothelial growth factor A, matrix metalloprotein-2, and -9. Additionally, the efficacy of Dio was inhibited by overexpression of STAT3. Finally, administration of Dio effectively suppressed the growth and angiogenesis of NSCLC tumors in mice (P<0.01).
Conclusions:
Dio potently inhibits tumor angiogenesis in vitro via Src/STAT3 pathway. It effectively attenuates tumor growth and suppresses angiogenesis in vivo. Given this, Dio is a promising anti-angiogenesis compound and might provide a novel strategy for the treatment of NSCLC.
Insights
Diosgenin (Dio) effectively inhibits lung cancer cell growth and tumor angiogenesis by targeting the Src/STAT3 pathway. This natural compound shows promise as a novel anti-angiogenesis strategy for non-small cell lung cancer (NSCLC) treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Lung cancer remains a leading cause of cancer-related mortality worldwide.
- Tumor angiogenesis, the formation of new blood vessels, is crucial for tumor growth and metastasis.
- Developing novel anti-angiogenic therapies is a critical area of cancer research.
Purpose of the Study:
- To investigate the anti-tumor and anti-angiogenic effects of diosgenin (Dio) in non-small cell lung cancer (NSCLC).
- To elucidate the underlying molecular mechanisms of Dio's action, particularly its impact on the Src/STAT3 pathway.
Main Methods:
- In vitro studies assessed Dio's effects on NSCLC cell apoptosis and proliferation using flow cytometry and colony formation assays.
- Transwell and angiogenesis assays evaluated Dio's impact on endothelial cell migration and vascular formation.
- Network pharmacology, molecular docking, and Western blot analyses explored Dio's mechanisms, focusing on the Src/STAT3 pathway and angiogenic factors.
- In vivo studies utilized mouse models (C57BL/6 and BALB/c-nu) to validate Dio's anti-tumor efficacy.
Main Results:
- Diosgenin significantly inhibited NSCLC cell growth and suppressed tumor angiogenesis in vitro (P<0.01).
- Network pharmacology and in vitro experiments confirmed Dio's anti-tumor and anti-angiogenic effects are mediated through the Src/STAT3 pathway.
- Dio inhibited the synthesis and secretion of key angiogenic factors, including VEGF-A, MMP-2, and MMP-9.
- Overexpression of STAT3 attenuated the efficacy of Dio.
- In vivo administration of Dio effectively suppressed NSCLC tumor growth and angiogenesis in mice (P<0.01).
Conclusions:
- Diosgenin potently inhibits tumor angiogenesis in vitro via the Src/STAT3 pathway.
- Dio effectively attenuates tumor growth and suppresses angiogenesis in vivo.
- Diosgenin is a promising anti-angiogenesis compound with potential as a novel therapeutic strategy for NSCLC.
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