肺癌转移仍然是癌症治疗中的重大挑战，需要探索新的治疗方式。水飞蓟素是一种从水飞蓟中提取的天然化合物，已被证明具有良好的抗癌特性。这项工作探讨了水飞蓟素对肺癌转移的抑制作用并揭示了潜在的过程，重点关注基质金属蛋白酶 (MMP) 2 和 MMP-9 活性。结合体外和分子对接分析，我们发现水飞蓟素通过调节 MMP-2 和 MMP-9 的表达，有效降低肺癌细胞的运动和侵袭。此外，MTT 测定显示水飞蓟素处理对细胞增殖具有剂量依赖性抑制作用，并发现 IC50 值为 58μM。我们观察到水飞蓟素治疗组的细胞凋亡形态特征。细胞周期分析显示细胞周期停滞在 G1 期，水飞蓟素处理组细胞凋亡增加 25.8%，如膜联蛋白 V 染色所证明的。此外，水飞蓟素治疗显示脂质过氧化水平升高，酶抗氧化水平降低，表明其在减轻氧化应激诱导细胞死亡方面的潜在作用。明胶酶谱分析表明水飞蓟素具有抑制肺癌中MMP-2和MMP-9表达的能力。此外，细胞迁移测定和集落形成测定表明，用水飞蓟素处理时，肺癌细胞的迁移和集落形成能力受损。分子对接研究进一步支持了水飞蓟素与MMP-2和MMP-9的结合亲和力，结合能分别为-10.26和-6.69kcal/mol。总的来说，我们的研究结果强调了水飞蓟素对肺癌转移的多方面抗癌特性，为其作为辅助治疗策略的治疗潜力提供了见解。© 2024 作者。

Lung cancer metastasis remains a significant challenge in cancer therapy, necessitating the exploration of novel treatment modalities. Silymarin, a natural compound derived from milk thistle, has demonstrated promising anticancer properties. This work explored the inhibitory effects of silymarin on lung cancer metastasis and revealed the underlying processes, focusing on matrix metalloproteinase (MMP) 2 and MMP-9 activities. Using a combination of in vitro and molecular docking analyses, we found that silymarin effectively reducing the lung cancer cells' motility and invasion by modulation of expression of MMP-2 and MMP-9. Furthermore, MTT assays revealed a dose-dependent inhibition of cell proliferation upon silymarin treatment and found the IC50 value at 58 μM. We observe that apoptotic morphology characteristic in silymarin treated groups. Cell cycle analysis exhibit the cell cycle arrest at G1 phase, 25.8 % increased apoptosis in silymarin treated groups, as evidenced by Annexin V staining. Moreover, silymarin treatment shows the lipid peroxidation in elevated level and reduced in enzymatic antioxidant level, indicating its potential role in mitigating oxidative stress induce cell death. Gelatin zymography assay indicates the silymarin has ability to inhibit the MMP-2 and MMP-9 expression in lung cancer. Additionally, cell migration assays and colony formation assays demonstrated impaired migratory and colony-forming abilities of lung cancer cells when treated with silymarin. Molecular docking studies further supported the binding affinity of silymarin with MMP-2 and MMP-9, demonstrate the -10.26 and -6.69 kcal/mol of binding energy. Collectively, our findings highlight the multifaceted anticancer properties of silymarin against lung cancer metastasis, providing insights into its therapeutic potential as an adjuvant treatment strategy.© 2024 The Authors.