title: Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4.
abstract: The epithelial-mesenchymal transition (EMT) is an important factor in lung cancer metastasis, and targeting EMT is a potential therapeutic strategy. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was abnormally elevated in many cancers. In this study, a traditional Chinese medicine ginsenoside Rg3 was used to investigate whether its inhibition to EMT and invasion of lung cancer is by the glycobiology mechanism. We found that Rg3 treatment (25, 50, 100 μg/ml) inhibited cell migration and invasion by wound-healing and transwell assays. Rg3 could significantly alter EMT marker proteins with increased E-cadherin, but decreased Snail, N-cadherin and Vimentin expression. Rg3 also down-regulated FUT4 gene and protein expression in lung cancer cells by qPCR, Western blot and immunofluorescence. After FUT4 down-regulated with shFUT4, EMT was obviously inhibited. Furthermore, the activation of EGFR through decreased LeY biosynthesis was inhibited, which blocked the downstream MAPK and NF-κB signal pathways. In addition, Rg3 reduced tumor volume and weight in xenograft mouse model, and significantly decreased tumor metastasis nodules in lung tissues by tail vein injection. In conclusion, Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer.
authors.affiliation: Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Tian
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning Province, China.
authors.forename: Dachuan
authors.initials: D
authors.lastname: Shen
authors.affiliation: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning Province, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Shan
authors.affiliation: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian Medical University, Dalian, Liaoning Province, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Liu
mesh_terms: D000072283:A549 Cells; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D016256:Lewis X Antigen / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D015820:Cadherins; D036145:Ginsenosides; D016256:Lewis X Antigen; D014746:Vimentin; C097367:ginsenoside Rg3; C066693:FUT4 protein, human; D005647:Fucosyltransferases
keywords: EGFR; EMT; FUT4; Rg3; lung cancer