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探索水飞蓟素对肺癌的抗癌和抗转移作用。

Exploring the anti-cancer and antimetastatic effect of Silymarin against lung cancer.

作者信息

Srinivasan Srithika, Mohanprasanth Aruchamy, Nadeem Ahmed, Saravanan Muthupandian

机构信息

Saveetha Medical College, Saveetha Institute of Medical and Technical Science (SIMATS), Chennai, India.

AMR and Nanotherapeutics Lab, Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Science (SIMATS), Chennai, India.

出版信息

Toxicol Rep. 2024 Sep 28;13:101746. doi: 10.1016/j.toxrep.2024.101746. eCollection 2024 Dec.

Abstract

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 IC 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.

摘要

肺癌转移仍然是癌症治疗中的一个重大挑战,因此有必要探索新的治疗方法。水飞蓟素是一种从水飞蓟中提取的天然化合物,已显示出有前景的抗癌特性。这项工作探索了水飞蓟素对肺癌转移的抑制作用,并揭示了其潜在机制,重点关注基质金属蛋白酶(MMP)2和MMP - 9的活性。通过体外实验和分子对接分析相结合的方法,我们发现水飞蓟素通过调节MMP - 2和MMP - 9的表达有效地降低了肺癌细胞的运动性和侵袭能力。此外,MTT分析显示水飞蓟素处理后细胞增殖呈剂量依赖性抑制,并发现其IC值为58μM。我们观察到水飞蓟素处理组具有凋亡形态特征。细胞周期分析显示细胞周期停滞在G1期,水飞蓟素处理组的细胞凋亡增加了25.8%,膜联蛋白V染色证明了这一点。此外,水飞蓟素处理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的细胞死亡中的潜在作用。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,细胞迁移实验和集落形成实验表明,水飞蓟素处理后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,证明其结合能为-10.26和-6.69 kcal/mol。总的来说,我们的研究结果突出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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21d9/11490676/09d700aae744/gr1.jpg

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