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由线粒体功能障碍驱动的AMPK-p53轴激活支了硫硫对抗肝细胞癌的影响

Xue Zheng¹, Yuhua Luo¹, Rui Huo¹

¹Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.

Scientific reports

|January 29, 2025

概括

一种新型化合物,PSCP,通过向硫代谢和激活AMPK-p53通路,显示出治疗肝细胞癌 (HCC) 的前景. 这种方法为肝癌治疗提供了一个新的策略.

科学领域:

在瘤学瘤学.
生物化学生物化学
分子生物学分子生物学

背景情况:

肝细胞癌 (HCC) 是一种抗化疗的原发性肝癌.
之前的硫硫化合物在HCC治疗中表现出有限的疗效.
一种新的,稳定的硫硫捐赠剂PSCP已经开发出来.

研究的目的:

研究PSCP对HCC的治疗作用.
阐明PSCP作用的潜在分子机制.
探索PSCP对硫代谢,p53,AMPK和HCC中的线粒体功能的影响.

主要方法:

蛋白质组 (CPTAC) 和转录组 (TCGA) 数据的生物信息学分析.
在体外和体内研究评估PSCP对HCC的影响.
对p53和AMP激活蛋白激酶 (AMPK) 途径的分析.
使用Autodock.com调查线粒体功能和PSCP的分子标.

主要成果:

在HCC中重新编程的硫代谢与预后不佳相关.
PSCP抑制了HCC瘤的生长,降低了细胞活力,并诱导了亡.
PSCP增加了p53表达和AMPK酸化,AMPK抑制减少了p53上调.
PSCP 损害了线粒体复合体 I 活性,可能向 Ndus3,ATP 补充对抗了细胞损伤.

结论:

硫代谢的重编程对于HCC的发展至关重要.
通过激活AMPK-p53信号轴,PSCP显示了治疗潜力.
在肝细胞癌治疗中,PSCP代表了一种有前途的新策略.

关键词:

这就是AMPKK.肝细胞癌是肝细胞癌.代谢重编程是一种代谢重编程.线粒体复合体是指线粒体复合体.硫硫酸盐的硫化物在 p53 里,p53 是一个 p53 的代码.

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