ZiyuglycosideⅡsuppressed the progression of osteosarcoma by coordinating estrogen-related receptor gamma and p53 signaling pathway  

作　　者：Hang Du Dongjin Wu Tianyu Zhang Ying Zhong Kaiyi Wu Xin Guo Lisong Sheng Nana Huang Chunzheng Gao Rong Sun 

机构地区：[1]The Second Hospital of Shandong University,Jinan 250033,China [2]Advanced Medical Research Institute,Shandong University,Jinan 250012,China [3]Academy of Traditional Chinese Medicine,Shandong University of Traditional Chinese medicine Jinan 250355,China [4]School of Pharmacy,Tianjin University of Traditional Chinese medicine,Tianjin 301617,China

出　　处：《Chinese Journal of Natural Medicines》2025年第3期354-367,共14页中国天然药物(英文版)

基　　金：supported by the National Key Research and Development Program of China(No.2022YFC3502100);the National Natural Science Foundation of China(No.82274197);the Cutting Edge Development Fund of Advanced Medical Research Institute Municipal Science and(No.GYY2023QY01);the Technology Project of Jinan City(No.202228099).

摘　　要：Osteosarcoma(OS)is the most prevalent primary malignant bone tumor affecting children and adolescents.Despite ongoing research efforts,the 5-year survival rate has remained stagnant for many years,highlighting the critical need for novel drug development to enhance current treatment protocols.ZiyuglycosideⅡ(ZYGⅡ),a triterpenoid saponin extracted from S.officinalis,has recently demonstrated antitumor properties.This study evaluates the antitumor effect of ZYGⅡon osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma(ESRRG),which inhibits disease progression.The research employs in vitro experiments using multiple established osteosarcoma cell lines,as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma.Additionally,ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYGⅡexerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53.Results indicate that ZYGⅡadministration led to decreased OS cell viability and reduced tumor volumes.Furthermore,cell cycles were arrested at the G_(0)/G1 phase,while the proportion of apoptotic cells increased.Expression of p53,ESRRG,p21,Bax,Cleaved Caspase-9,and Cleaved Caspase-3 proteins increased,while expression of CDK4,Cyclin D1,and Bcl-2 proteins decreased.Multiple ZYGⅡand ESRRG docking patterns were simulated through molecular docking.Comparing the pharmacodynamic response of ZYGⅡto OS cell lines with reduced ESRRG and normal expression demonstrated that ZYGⅡinhibits osteosarcoma progression,induces cell cycle arrest,and promotes cell apoptosis through the coordination of p53 and ESRRG.In conclusion,ZYGⅡinhibits osteosarcoma progression,leads to cell cycle arrest,and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.

关 键 词：ZiyuglycosideⅡ OSTEOSARCOMA Cell cycle arrest P53 Estrogen-related receptor gamma 

分 类 号：R73[医药卫生—肿瘤]