Erianin inhibits the proliferation of lung cancer cells by suppressing mTOR activation and disrupting pyrimidine metabolism  

作　　者：Lili Yan Yanfen Liu Yufei Huang Xiaoyu Sun Haiyang Jiang Jie Gu Jing Xia Xueni Sun Xinbing Sui 

机构地区：[1]School of Pharmacy and Department of Medical Oncology,The Affiliated Hospital of Hangzhou Normal University,Hangzhou Normal University,Hangzhou 311121,China [2]Department of Gastrointestinal&Pancreatic Surgery,Key Laboratory of Gastroenterology of Zhejiang Province,Zhejiang Provincial People’s Hospital,Affiliated People’s Hospital,Hangzhou Medical College,Hangzhou 310014,China

出　　处：《Cancer Biology & Medicine》2025年第2期144-165,共22页癌症生物学与医学(英文版)

基　　金：supported by the National Natural Science Foundation of China(82104207);Natural Science Foundation of Zhejiang Province(LQ22H280001)。

摘　　要：Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,remain poorly understood and necessitate further investigation.Methods:Lung cancer cell viability was evaluated using the CCK-8 assay.Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression.m RNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes.Potential targets were identified and validated through molecular docking and Western blot analysis.The roles of mammalian target of rapamycin(m TOR)and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase(CAD)in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement.Additionally,lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin in vivo.Results:Erianin significantly inhibits the proliferation of lung cancer cells,induces apoptosis,and causes G2/M phase cell cycle arrest.Integrative analysis of m RNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells.Notably,uridine supplementation mitigated the inhibitory effects of erianin,establishing a connection between pyrimidine metabolism and anticancer activity.Network pharmacology analyses identified m TOR as a key target of erianin.Erianin inhibited m TOR phosphorylation,thereby blocking downstream effectors(S6K and CAD),which are essential regulators of pyrimidine metabolism.Conclusions:Erianin is a promising therapeutic candidate for lung cancer.Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing m TOR activation.

关 键 词：ERIANIN anti-cancer property lung cancer MTOR pyrimidine metabolism 

分 类 号：R285[医药卫生—中药学]