title: Celecoxib downregulates CD133 expression through inhibition of the Wnt signaling pathway in colon cancer cells.
abstract: CD133-positive cancer stem cells in colon cancer are resistant to conventional chemotherapy. The aim of the present study was to investigate the effect of celecoxib, a COX-2 inhibitor, on CD133 expression in HT29 and DLD1 cells. HT29 and DLD1 cells were treated with celecoxib using different concentrations and duration. CD133 expression was detected by flow cytometry, Western blotting, immunofluorescence, and quantitative real-time PCR. Wnt signaling pathway activity was measured by luciferase assay and gene expression changes were monitored using microarray analysis. HT29 cells showed significantly decreasing levels of CD133 expression with increasing concentrations of or duration of exposure to celecoxib. CD133 mRNA relative expression in HT29 and DLD1 cells also decreased with drug exposure. Furthermore, Wnt activation in HT29 and DLD1 cells decreased with celecoxib treatment. Gene expression microarray showed stemness genes, including Lgr5, Oct4, Prominin-1, Prominin-2, CXCR4, E2F8, CDK-2, were downregulated and differentiation genes, including CEACAM5, GDF, ADFP, ICAM1, were upregulated. Our results show that CD133 expression was downregulated by celecoxib through inhibition of the Wnt signaling pathway, which may be lead to cell differentiation.
authors.affiliation: Department of Medical Oncology, Gastrointestinal Hospital, Sun Yatsen University, China. dengyanh@mail.sysu.edu.cn
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Deng
authors.forename: Qiao
authors.initials: Q
authors.lastname: Su
authors.forename: Jianwen
authors.initials: J
authors.lastname: Mo
authors.forename: Xinhui
authors.initials: X
authors.lastname: Fu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Edward H
authors.initials: EH
authors.lastname: Lin
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D000068579:Celecoxib; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000235:genetics; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D052246:Cyclooxygenase 2 Inhibitors; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D000068579:Celecoxib