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Resveratrol Suppresses Lung Cancer through the NLRP3/IL-1β Signaling Axis to Improve Immune Microenvironment
Hongting Sui1, Zhiguo Lin2, Xiaodie Zheng3
1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Qiqihar Medical University; zhile1968@yeah.net.
Abstract:
The incidence and mortality rates of lung cancer remain high, posing a serious threat to human health. This study aims to investigate the role of resveratrol in lung cancer and its regulatory mechanism on the immune microenvironment. Human lung cancer A549 cells were treated with different concentrations of resveratrol, and a syngeneic mouse model of lung cancer was established to evaluate the effects of resveratrol and the NLRP3 inhibitor MCC950 on cell growth and the expression of NLRP3/IL-1β. Meanwhile, tumor growth, cell apoptosis, T cell infiltration, and the expression of key signaling proteins were examined in vivo. The results showed that resveratrol significantly inhibited the proliferation of A549 cells, induced cell cycle arrest and apoptosis, and was accompanied by reduced expression of NLRP3 and IL-1β. In the syngeneic mouse model of lung cancer, resveratrol treatment suppressed tumor cell proliferation, improved tumor morphology, enhanced T lymphocyte infiltration, and concurrently decreased the expression of NLRP3, IL-1β, ASC, and cleaved-caspase-1. These findings indicate that resveratrol inhibits tumor growth and remodels the immune microenvironment by targeting the NLRP3/IL-1β signaling axis, offering new insights and potential strategies for lung cancer immunotherapy.
Insights
Resveratrol effectively inhibits lung cancer cell growth and apoptosis by targeting the NLRP3/IL-1β pathway. This natural compound also remodels the tumor immune microenvironment, offering potential for lung cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Lung cancer presents high incidence and mortality rates globally.
- Understanding the tumor immune microenvironment is crucial for effective cancer therapy.
Purpose of the Study:
- To investigate the anti-cancer effects of resveratrol in lung cancer.
- To elucidate resveratrol's mechanism in regulating the tumor immune microenvironment via the NLRP3/IL-1β signaling pathway.
Main Methods:
- In vitro: Human lung cancer A549 cells treated with resveratrol.
- In vivo: Syngeneic mouse model of lung cancer treated with resveratrol and MCC950 (NLRP3 inhibitor).
- Assessed cell proliferation, apoptosis, cell cycle, T cell infiltration, and protein expression (NLRP3, IL-1β, ASC, cleaved-caspase-1).
Main Results:
- Resveratrol inhibited A549 cell proliferation, induced cell cycle arrest and apoptosis, and reduced NLRP3/IL-1β expression.
- In vivo, resveratrol suppressed tumor growth, improved tumor morphology, and enhanced T lymphocyte infiltration.
- Resveratrol treatment decreased NLRP3, IL-1β, ASC, and cleaved-caspase-1 expression in the tumor microenvironment.
Conclusions:
- Resveratrol exhibits anti-lung cancer properties by inhibiting tumor cell proliferation and inducing apoptosis.
- Resveratrol remodels the immune microenvironment by targeting the NLRP3/IL-1β signaling axis.
- Resveratrol presents a promising therapeutic strategy for lung cancer immunotherapy.
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