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通过AMPK诱导的异黄素诱导的ER压力通过AMPK增强OSCC中的化学敏感性

J Yao¹, S Song¹, T Liu¹

¹State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Research Unit of Oral Carcinogenesis and Management & Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Journal of dental research

|March 12, 2025

概括

伊索瓜诺辛 (isoG) 通过激活AMPK,诱导ER压力并改善化疗敏感度来增强口腔癌的治疗效果. 一个新的基于isoG的平台与5-FU相结合,在临床前模型中显示出显著的瘤抑制.

科学领域:

生物化学生物化学
在瘤学瘤学.
材料科学材料科学材料科学

背景情况:

口腔状细胞癌 (OSCC) 的治疗选择有限.
伊索瓜诺辛 (isoG) 显示出抗OSCC的潜力,但其机制尚不清楚.
开发OSCC的新型治疗策略至关重要.

研究的目的:

在OSCC中阐明异黄素 (isoG) 的抗瘤机制.
调查isoG在调节化学敏感性的作用.
为OSCC开发和评估一种基于isoG的新型治疗平台.

主要方法:

研究了isoG的代谢物,异黄5'-单酸盐 (isoGMP),以及其对内分泌网膜 (ER) 应激和腺单酸盐激活蛋白激酶 (AMPK) 激活的影响.
评估了isoG和5-fluorouracil (5-FU) 对OSCC细胞的联合作用.
开发了一种isoG-phenylenediboronic acid-isoG (isoGPBisoG) 结构,并在OSCC异种移植模型中评估其与5-FU结合的疗效.

主要成果:

IsoG的抗增殖作用由isoGMP介导,通过AMPK激活诱导ER压力和细胞死亡.
通过isoG激活AMPK可增强OSCC细胞对5-FU的敏感性,从而产生协同作用的抗癌效应.
在OSCC异种移植模型中,isoGPBisoG和5-FU组合显示出显著的瘤抑制 (71.0%和56.6%).

结论:

伊索瓜诺辛 (isoG) 是通过AMPK激活在OSCC中强烈增强化疗效的强效增强剂.
isoGPBisoG和5-FU组合代表了OSCC一个有前途的协同治疗平台.
这种新的方法为开发更有效的OSCC治疗提供了新的方向.

关键词:

这是一种抗癌药物.药物输送是药物输送的过程.这是一种水凝.isoG isoG是什么意思在 isoGMP 的基础上,isoGMP 是地方行政,地方行政.

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