Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment  

作　　者：Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen 

机构地区：[1]Department of Sport Medicine,Huashan Hospital,Fudan University,Shanghai,China [2]Department of Orthopedic Surgery,Hainan Province Clinical Medical Center,Haikou Affiliated Hospital of Central South University Xiangya School of Medicine,Haikou,Hainan Province,China [3]Department of Basic Medicine,Shanghai Jiao Tong University School of Medicine,Shanghai Jiao Tong University,Shanghai,China [4]Department of Neurosurgery,Second Affiliated Hospital of Zhejiang University School of Medicine,Zhejiang University,Hangzhou,Zhejiang Province,China [5]Department of Orthopedics,Shanghai General Hospital,School of Medicine Shanghai Jiao Tong University,Shanghai,China [6]Department of Infectious Diseases,Children’s Hospital of Fudan University,National Children’s Medical Center,Shanghai,China [7]Department of Rehabilitation,The Second Affiliated Hospital of Shandong First Medical University,Taian,Shandong Province,China

出　　处：《Neural Regeneration Research》2025年第4期1135-1152,共18页中国神经再生研究（英文版）

基　　金：supported by Project of the Health Shanghai Initiative Special Fund(Medical-Sports Integration,Creating a New Model of Exercise for Health),No.JKSHZX-2022-02(to SC).

摘　　要：Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关 键 词：exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise 

分 类 号：R739.41[医药卫生—肿瘤]