Silencing ribosomal protein L4 enhances the inhibitory effects of triptolide on non-small cell lung cancer cells by disrupting the mouse double minute 2 protein–P53 tumor suppressor pathway  

作　　者：NAN TANG YAJING ZHAN JIAYAN MAO ANKANG YIN WEI WANG JUAN WANG 

机构地区：[1]School of Medical Technology and Information Engineering,Zhejiang Chinese Medical University,Hangzhou,310053,China [2]Zhejiang Chinese Medical University,Hangzhou,310053,China [3]Department of Clinical Laboratory,Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province,Zhejiang Academy of Traditional Chinese Medicine,Tongde Hospital of Zhejiang Province,Hangzhou,310012,China

出　　处：《BIOCELL》2023年第9期2009-2026,共18页生物细胞（英文）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.82004007 and 81774026).

摘　　要：Non-small cell lung cancer(NSCLC)is a malignant tumor with high incidence worldwide.Triptolide(TP),extracted from Tripterygium wilfordii Hook F,exhibits potent broad-spectrum antitumor activity.Although some mechanisms through which TP inhibits NSCLC are well understood,those that involve ribosomal proteins remain yet to be understood.In this study,the transcriptome and proteome were integrated and analyzed.Our data indicated ribosomal protein L4(RPL4)to be a core hub protein in the protein-protein interaction network.RPL4 is overexpressed in NSCLC tissues and cells.Transfection with siRPL4 or TP treatment alone arrested the cell cycle in the G1 phase,induced cell apoptosis,and repressed cell invasion.Compared to treating cells with TP alone or siRPL4,treating them with siRPL4–TP enhanced the inhibition of NSCLC cells.Reduced RPL4 expression reinforced the inhibitory effects of TP on NSCLC cells by disrupting the MDM2-P53 pathway and by altering the expression of PARP1/Snail/cyclin D1.In vivo assays verified that TP induced cell apoptosis and reduced RPL4 expression in xenografts.These findings provide clues to facilitate the development of effective TP-based therapeutic strategies to kill NSCLC cells.

关 键 词：NSCLC RPL4 TRIPTOLIDE Proteomics Transcriptome 

分 类 号：R734.2[医药卫生—肿瘤]