Abstract：
Se-methylselenocysteine (MSC) is recognized for its potential in cancer prevention, yet the specific effects and underlying processes it initiates within non-small cell lung cancer (NSCLC) remain to be fully delineated. Employing a comprehensive array of assays, including CCK-8, colony formation, flow cytometry, MitoSOX Red staining, wound healing, transwell, and TUNEL staining, we evaluated MSC\'s effects on A549 and 95D cell lines. Our investigation extended to the ROS-mediated NF-κB signaling pathway, utilizing Western blot analysis, P65 overexpression, and the application of IκB-α inhibitor (BAY11-7082) or N-acetyl-cysteine (NAC) to elucidate MSC\'s mechanism of action. In vivo studies involving subcutaneous xenografts in mice further confirmed MSC\'s inhibitory effect on tumor growth. Our findings indicated that MSC inhibited the proliferation of A549 and 95D cells, arresting cell cycle G0/G1 phase and reducing migration and invasion, while also inducing apoptosis and increasing intracellular ROS levels. This was accompanied by modulation of key proteins, including the upregulation of p21, p53, E-cadherin, Bax, cleaved caspase-3, cleaved-PARP, and downregulation of CDK4, SOD2, GPX-1. MSC was found to inhibit the NF-κB pathway, as evidenced by decreased levels of P-P65 and P-IκBα. Notably, overexpression of P65 and modulation of ROS levels with NAC could attenuate MSC\'s effects on cellular proliferation and metastasis. Moreover, MSC significantly curtailed tumor growth in vivo and disrupted the NF-κB signaling pathway. In conclusion, our research demonstrates that MSC exhibits anticancer effects against NSCLC by modulating the ROS/NF-κB signaling pathway, suggesting its potential as a therapeutic agent in NSCLC treatment.
摘要：
硒-甲基硒代半胱氨酸（MSC）因其在癌症预防中的潜力而被认可，然而,它在非小细胞肺癌(NSCLC)中引发的具体效应和潜在过程仍有待完全描述.采用一系列全面的检测方法，包括CCK-8，集落形成，流式细胞术,MitoSOX红染色,伤口愈合，transwell,和TUNEL染色，我们评估了MSC对A549和95D细胞系的影响。我们的研究扩展到ROS介导的NF-κB信号通路，利用蛋白质印迹分析，P65过表达，并应用IκB-α抑制剂(BAY11-7082)或N-乙酰半胱氨酸(NAC)阐明MSC的作用机制。涉及小鼠皮下异种移植物的体内研究进一步证实了MSC对肿瘤生长的抑制作用。我们的发现表明，MSC抑制A549和95D细胞的增殖，阻止细胞周期G0/G1期，减少迁移和侵袭，同时还诱导细胞凋亡和增加细胞内ROS水平。这伴随着关键蛋白质的调节，包括p21，p53，E-cadherin，Bax,裂解的caspase-3，裂解的PARP，以及CDK4、SOD2、GPX-1的下调。发现MSC抑制NF-κB途径，P-P65和P-IκBα水平降低证明。值得注意的是,P65的过表达和NAC对ROS水平的调节可以减弱MSC对细胞增殖和转移的影响。此外，MSC显著减少了体内肿瘤生长并破坏了NF-κB信号通路。总之,我们的研究表明，MSC通过调节ROS/NF-κB信号通路对NSCLC表现出抗癌作用，提示其作为非小细胞肺癌治疗药物的潜力。
