伊索拉姆尼丁通过诱导细胞循环停止,对与癌症相关的纤维细胞产生抗增殖作用
Munkhzul Ganbold1, Pakavarin Louphrasitthiphol2, Takafumi Miyamoto3
1Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Science and Technology (AIST), Tsukuba, Japan.
概括
伊索拉姆尼丁 (ISO) 通过抑制与癌症相关的纤维细胞 (CAF) 来表现出抗癌性质. 这种饮食中的黄胺诱导细胞循环停止并减少炎症,这表明组合性癌症治疗的潜力.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 与癌症相关的纤维细胞 (CAFs) 在胰腺管道腺癌 (PDAC) 中促进瘤生长和化学抵抗.
- 调节CAF是一种有前途的策略,可以提高癌症治疗效率.
- 饮食中含有的黄类化合物伊索拉姆尼丁 (ISO) 具有抗氧化,抗癌和抗炎性质.
研究的目的:
- 调查伊索拉姆尼丁 (ISO) 对胰腺管道腺癌衍生CAF的抗增殖作用.
- 为了阐明ISO处理的CAF的转录形状.
- 探索ISO在向瘤微环境方面的潜力.
主要方法:
- 细胞活力测试以评估ISO的抗增殖作用.
- 微阵列分析以确定ISO处理的CAF中的转录组变化.
- 细胞周期分析,p53通路基因表达,线粒体功能测定 (膜潜力,ATP生产,氧消耗率) 和炎症基因表达分析.
主要成果:
- 国际标准组织 (ISO) 证实了CAF生存能力的时间和度依赖性下降以及亡的轻微增加.
- 在G2/M阶段的ISO诱导细胞循环停止,与p53通路基因的上调和细胞循环/DNA复制通路的下调.
- ISO损害了线粒体平衡,降低了ATP的产生,并显著抑制了关键炎症基因 (IL1A1,IL6,CXCL1,LIF) 的表达.
结论:
- 伊索哈姆尼丁通过诱导G2/M细胞周期停止,激活p21,破坏线粒体平衡,并抑制炎症介质,对人类CAF产生细胞静止作用.
- 这些发现突显了ISO作为治疗剂的潜力,该药物既针对癌细胞,也针对瘤微环境.
- 需要进一步的研究来探索ISO在组合性癌症治疗策略中的作用.
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