普伦巴丁通过调节与p53相关的SLC7A11表达来诱导结肠癌细胞中的铁亡
Bingyi Wang1, Weiqi Kong1, Lixin Lv2
1Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Heliyon
|April 10, 2024
概括
普伦巴丁通过p53通路降低SLC7A11的调节,诱导结肠癌细胞中的铁亡. 这种天然化合物抑制了癌细胞的增殖和入侵,提供了潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 自然产品 化学 化学
背景情况:
- 结肠癌仍然是一个重大的全球健康挑战.
- 识别具有独特作用机制的新型治疗剂对于改善患者的治疗结果至关重要.
- 细胞死亡的受控形式铁亡已成为癌症治疗中的一个有希望的目标.
研究的目的:
- 阐明plumbagin在结肠癌细胞中诱导铁亡的机制.
- 为了研究p53信号通路和SLC7A11在plumbagin介导的铁亡中的作用.
- 评估plumbagin在体外和体外的抗癌作用.
主要方法:
- 细胞活力测试 (CCK-8),殖民地形成和Transwell测试被用于评估扩散和入侵.
- 对结肠癌细胞系中的铁亡标记物 (Fe2+,GSH,GPX4) 和关键蛋白 (p53,SLC7A11) 的分析.
- 使用携带瘤的裸体小鼠模型进行体内研究,以评估带有和没有p53沉默的plumbagin的疗效.
主要成果:
- 普伦巴丁显著抑制了结肠癌细胞的扩散,入侵和殖民地形成.
- 通过增加Fe2+和降低GSH和GPX4水平,plumbagin诱导了铁亡.
- 普伦巴丁促进了p53酸化,并抑制了SLC7A11的表达,这些效应被p53沉默或铁灭抑制所逆转.
结论:
- 普伦巴丁有效地诱导结肠癌细胞中的铁亡.
- 该机制涉及p53介导的SLC7A11下调,导致抑制的增殖和入侵.
- 普伦巴金证明了结肠癌治疗的治疗潜力.
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