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有氧运动预调剂通过PI3K/AKT驱动的代谢表观遗传重编程和免疫微环境重塑来抑制皮下瘤发生
Xue Zhang1, Yixue Xia2, Lingbing Zheng2
1School of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, China; School of Physical Education and Health, East China Normal University, Shanghai 200241, China; School of Kinesiology, Shanghai University of Sport, Shanghai 200438, China.
有氧运动预先调节通过降低葡萄糖代谢基因的调节和减少M1巨细胞透来抑制皮下瘤生长. 这种抗瘤效应与通过PI3K/AKT通路的表观遗传重编程有关.
科学领域:
- 在瘤学瘤学.
- 运动生理学 运动生理学
- 分子生物学分子生物学
背景情况:
- 众所周知,有氧运动可以抑制瘤,有氧糖解与瘤发展有关.
- 运动预先条件对皮下瘤生长的影响及其潜在机制需要进一步研究.
研究的目的:
- 调查有氧运动预条件对小鼠皮下瘤生长的影响.
- 阐明运动影响瘤代谢和生长的分子机制.
主要方法:
- 在皮下移植Hepa1-6细胞之前,小鼠接受了12周的有氧运动.
- 对瘤组织进行了基因表达分析 (RNA-Seq),西部斑,免疫光和DNA甲基化分析.
- 分析包括评估葡萄糖代谢标志物 (PKM2,GLUT1,LDHA,HK2),PI3K/AKT通路激活,免疫细胞透和表观遗传修饰.
主要成果:
- 与对照组相比,有氧预调剂显著抑制了Hepa1-6瘤的生长.
- 运动降低了关键葡萄糖代谢基因的表达和下调PI3K/AKT通路蛋白 (P-PI3K,P-AKT).
- 运动减少了M1巨细胞的透,并且与HCC模型中的PI3K/Akt路径中的肝脏DNA甲基化变化有关.
结论:
- 有氧运动预先调节通过表观遗传重新编程瘤代谢,主要通过PI3K/AKT途径,产生抗瘤效应.
- 运动诱导的瘤生长抑制包括降低葡萄糖代谢的调节和瘤免疫微环境的调节.
- PI3K/AKT通路作为运动调节瘤代谢和生长的中心调解器.
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