Department of Integrated Traditional Chinese and Western Medicine, Xiangtan Central Hospital, Xiangtan, China.
Research Institute for Future Food, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region, Hong Kong, China.
Kaohsiung J Med Sci. 2023 Nov;39(11):1106-1118. doi: 10.1002/kjm2.12752. Epub 2023 Sep 12.
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.
非小细胞肺癌（NSCLC）约占所有肺癌病例的 85%。荷叶碱被用作具有多种药理作用的中药，包括抗肿瘤作用；然而，尚未有报道表明荷叶碱通过引起 NSCLC 细胞发生细胞焦亡来发挥抗癌作用。我们使用两种典型的肺癌细胞系 A549 和 H1299 以及 42 个肺癌组织样本，研究荷叶碱对 TGF-β 和 MST1 的调节作用。我们还使用不同浓度的荷叶碱处理肺癌细胞，研究其对肺癌细胞存活、迁移、侵袭和上皮-间充质转化（EMT）以及细胞焦亡的影响。采用慢病毒介导的 TGF-β 和 MST1 的功能获得性研究来验证 TGF-β 和 MST1 在肺癌中的作用。接下来，我们使用小鼠移植肿瘤模型来评估荷叶碱处理对肺癌组织转移能力的影响。随着荷叶碱浓度的增加，A549 和 H1299 细胞的活力、迁移、侵袭和 EMT 能力下降，而细胞焦亡增加。荷叶碱抑制 TGF-β 的表达来调节 MST1 诱导的活性氧（ROS）的产生。在体外或小鼠移植 A549 细胞中过表达 TGF-β 恢复了荷叶碱对肿瘤发展的抑制作用。过表达 MST1 明显增强了细胞焦亡。荷叶碱通过下调 TGF-β 来调节 MST1 表达从而诱导 ROS 形成，促进细胞焦亡。因此，我们的研究表明荷叶碱可以作为 NSCLC 患者的辅助治疗药物。
