拉福克桑胺负面调节STAT3和NF-κB活性以及与炎症相关的结肠瘤发生
Teresa Pacifico1, Carmine Stolfi1, Lorenzo Tomassini1
1Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
Cancer science
|September 6, 2024
概括
药物rafoxanide抑制了关键的癌症通路,信号转换器和转录3 (STAT3) 和核因子-κB (NF-κB) 的激活剂,以减少与炎症相关的结直肠癌 (CRC) 的生长,而不会损害健康细胞.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药物重用 药物重用
背景情况:
- 信号转换器和转录3 (STAT3) 和核因子-κB (NF-κB) 的激活器在结直肠癌 (CRC) 中过度激活,促进瘤生长和炎症.
- 甲虫药物拉福克桑伊德通过药物重新定位显示出作为抗癌剂的潜力.
研究的目的:
- 调查rafoxanide在调节STAT3/NF-κB通路和CRC炎症中的潜力.
- 在临床前CRC模型中评估rafoxanide的抗瘤作用.
主要方法:
- 使用了与大肠炎相关的CRC的小鼠模型.
- 在CRC细胞中评估了STAT3 / NF-κB激活,细胞增殖和细胞因子产生,患者衍生的扩展体/器官,以及用rafoxanide治疗的瘤透白细胞 (TILs).
- 评估了拉福克桑胺治疗的TILs对CRC细胞行为的影响.
主要成果:
- 拉福克桑胺有效抑制STAT3 / NF-κB激活和炎症驱动的结肠瘤发生 in vivo.
- 该药物降低了CRC细胞,扩展体,有机体和TILs中的STAT3 / NF-κB激活.
- 拉福克桑胺损害了TILs产生前瘤细胞因子和促进CRC细胞增殖的能力,没有观察到对正常肠道细胞的影响.
结论:
- 拉福克萨尼德在CRC微环境中对STAT3/NF-κB瘤活性表现出一种新的多层次抑制作用.
- 拉福克萨尼德是炎症相关结直肠癌的有希望的治疗候选者.
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