PO.TB03.01 · 肿瘤生物学
三萜类薯蓣皂苷元对肺癌细胞的抗转移特性
Anti-metastatic properties of the triterpene diosgenin on lung carcinoma cells
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
肺癌仍是全球癌症相关死亡的首要原因，非小细胞肺癌（NSCLC）约占所有病例的85%。虽然化疗是一种标准治疗选择，但其成功因剂量依赖性毒性和化疗耐药的发生而受限。这些挑战增加了对植物化学物质（如三萜类）的兴趣，三萜是具有广泛药理活性和潜在抗癌特性的天然代谢产物。薯蓣皂苷元（Dios）是一种存在于众多药用植物中的甾体三萜，据报道可调节对癌细胞存活和转移至关重要的通路。本研究评估了薯蓣皂苷元对NSCLC细胞的影响，以阐明其作用机制。薯蓣皂苷元在24小时内以剂量依赖方式在微摩尔范围内表现出强细胞毒活性。功能实验显示，薯蓣皂苷元显著抑制A549细胞迁移，并诱导细胞周期停滞在S期和G2/M期。蛋白质分析揭示增殖和存活标志物的表达降低，包括Ki67、MAPK和PI3K，同时Caspase 3/7活化显著增加。转移相关基因表达谱显示，薯蓣皂苷元下调了关键的促转移基因，如MMP2、MMP9和PREX1，这些基因均参与细胞外基质降解、细胞骨架重塑和侵袭潜能。相比之下，薯蓣皂苷元上调了NDRG1，这是一个公认的转移抑制因子，参与抑制上皮-间质转化并限制细胞运动性。总的来说，这些发现表明薯蓣皂苷元通过抑制增殖、诱导凋亡和显著削弱转移相关通路来发挥多靶点抗癌活性。薯蓣皂苷元是一种有前景的天然治疗候选物，可减缓NSCLC进展并降低转移潜能。
致谢：本研究得到美国国立卫生研究院国立综合医学科学研究所机构发展奖（IDeA）的支持，资助编号为P20GM103475。
查看英文原文 English abstract
Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung carcinoma (NSCLC) accounting for ~85% of all cases. Although chemotherapy is a standard treatment option, its success is limited by dose-dependent toxicity and the development of chemoresistance. These challenges have increased interest in phytochemicals such as triterpenes, natural metabolites with broad pharmacological activities and potential anticancer properties. Diosgenin (Dios), a steroidal triterpene present in numerous medicinal plants, has been reported to modulate pathways central to cancer cell survival and metastasis. This study evaluated the effects of Diosgenin on NSCLC cells to elucidate its mechanism of action. Diosgenin demonstrated strong cytotoxic activity in the micromolar range in a dose-dependent manner within 24 hours. Functional assays showed that Diosgenin significantly inhibited A549 cell migration and induced cell cycle arrest at the S and G2/M phases. Protein analysis revealed reduced expression of proliferative and survival markers, including Ki67, MAPK, and PI3K, accompanied by a notable increase in Caspase 3/7 activation. Metastasis-related gene expression profiling showed that Diosgenin downregulated key pro-metastatic genes such as MMP2, MMP9, and PREX1, all of which contribute to extracellular matrix degradation, cytoskeletal remodeling, and invasive potential. In contrast, Diosgenin upregulated NDRG1, a well-established metastasis suppressor involved in inhibiting epithelial-to-mesenchymal transition and limiting cell motility. Collectively, these findings indicate that Diosgenin exerts multi-targeted anticancer activity by suppressing proliferation, inducing apoptosis, and significantly impairing metastasis-associated pathways. Diosgenin represents a promising natural therapeutic candidate for slowing NSCLC progression and reducing metastatic potential.
Acknowledgement: This research was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103475.
利益披露 Disclosure
L. M. Santos, None..
E. Figueroa, None..
J. Figueroa, None..
D. Pérez, None..
Y. Ferrer, None.