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Neferine inhibits the development of lung cancer cells by downregulating TGF-β to regulate MST1/ROS-induced
Peng-Cheng Zhong1, Zhi-Wen Liu2, Qi-Chang Xing3
1Department of Integrated Traditional Chinese and Western Medicine, Xiangtan Central Hospital, Xiangtan, China.
Abstract:
Non-small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF-β and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial-mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus-mediated gain-of-function studies of TGF-β and MST1 were applied to validate the roles of TGF-β and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF-β expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF-β in either in vitro or mouse-transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF-β to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients.
Insights
Neferine, a traditional Chinese medicine, induces pyroptosis in non-small cell lung cancer (NSCLC) cells by regulating MST1 and TGF-β pathways. This finding suggests neferine
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Non-small cell lung cancer (NSCLC) is the most common type of lung cancer.
- Neferine, a traditional Chinese medicine, exhibits antitumor properties.
- The role of neferine in inducing pyroptosis in NSCLC remains unexplored.
Purpose of the Study:
- To investigate the effect of neferine on NSCLC cell survival, migration, invasion, epithelial-mesenchymal transition (EMT), and pyroptosis.
- To elucidate the regulatory mechanisms of neferine involving TGF-β and MST1 pathways.
- To evaluate the therapeutic potential of neferine in preclinical models of NSCLC.
Main Methods:
- Cell culture of A549 and H1299 NSCLC lines.
- Treatment with varying concentrations of neferine.
- Lentivirus-mediated gain-of-function studies for TGF-β and MST1.
- Murine transplanted tumor models.
- Assessment of cell viability, migration, invasion, EMT, and pyroptosis.
Main Results:
- Neferine decreased NSCLC cell viability, migration, invasion, and EMT.
- Neferine increased pyroptosis in NSCLC cells.
- Neferine downregulated TGF-β, modulating MST1-induced reactive oxygen species (ROS) production.
- Overexpression of TGF-β reversed neferine's inhibitory effects, while MST1 overexpression enhanced pyroptosis.
Conclusions:
- Neferine induces pyroptosis in NSCLC by regulating MST1 expression via TGF-β downregulation and ROS generation.
- Neferine demonstrates potential as an adjuvant therapy for NSCLC.
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