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作 者:Qiang Wang Canfeng Fan Gen Tsujio Takashi Sakuma Koji Maruo Yurie Yamamoto Daiki Imanishi Kyoka Kawabata Hinano Nishikubo Saki Kanei Rika Aoyama Syuhei Kushiyama Masaichi Ohira Masakazu Yashiro
机构地区:[1]Department of Molecular Oncology and Therapeutics,Osaka Metropolitan University Graduate School of Medicine,Osaka 545-0051,Japan [2]Cancer Center for Translational Research,Osaka Metropolitan University Graduate School of Medicine,Osaka 545-0051,Japan [3]Department of Gastroenterological Surgery,Osaka Metropolitan University Graduate School of Medicine,Osaka 545-0051,Japan
出 处:《World Journal of Experimental Medicine》2025年第2期130-141,共12页世界实验医学杂志(英文)
摘 要:BACKGROUND Gallbladder cancer(GBC)is a highly aggressive malignant tumor originating from the biliary tract.As one of the most common malignancies in the biliary system,GBC is particularly challenging due to its tendency to remain asymptomatic,which often results in delayed diagnoses even at advanced stages.Combined with its invasive potential and poor response to conventional therapies,GBC has a high mortality rate,highlighting the critical need for innovative therapeutic approaches.Identifying molecular biomarkers for early detection and discovering novel therapeutic targets might be essential to improving outcomes of patients with GBC.AIM To establish a novel GBC cell line to investigate the molecular mechanisms underlying GBC progression and evaluate potential therapeutic targets.METHODS We developed a unique GBC cell line,named OCUG-2,derived from a metastatic peritoneal implant,and verified its authenticity using short tandem repeat(STR)profiling.RT-PCR and RNA sequencing(RNA-seq)were performed to assess gene expression profiles,with functional enrichment analyzed through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses.The MTT cell proliferation assay and an invasion assay were performed to evaluate response to nine inhibitors.Immunohistochemistry(IHC)was conducted on 34 GBC samples to analyze insulin-like growth factor 1 receptor(IGF1R)expression.RESULTS OCUG-2 cells displayed adhesive growth with dendritic morphology and a 30-hour doubling time.Subcutaneous inoculation of OCUG-2 cells into mice confirmed their tumorigenic potential.STR analysis authenticated the cell line,and there was high mRNA and protein expression of IGF1R in OCUG-2 cells.The IGF1R inhibitor picropodophyllotoxin significantly inhibited OCUG-2 cell proliferation,yielding an IC50 of 0.49μM.RNA-seq analysis identified gene fusions,and GO/KEGG functional enrichment analyses revealed pathways implicated in cancer progression.IHC analysis showed IGF1R positivity in 18 of 34 GBC cases,with significant asso
关 键 词:Gallbladder cancer Cell line Insulin-like growth factor 1 receptor Molecular target Mouse model
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