Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4
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Lili Tian1,*, Dachuan Shen2,*, Xiaodong Li2, Xiu Shan1, Xiaoqi Wang3, Qiu Yan4 and Jiwei Liu1
1 Department of Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
2 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning Province, China
3 Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
4 Department of Biochemistry and Molecular Biology, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian Medical University, Dalian, Liaoning Province, China
* These authors have contributed equally to this work
Qiu Yan, email:
Jiwei Liu, email:
Keywords: Rg3, EMT, FUT4, EGFR, lung cancer
Received: May 05, 2015 Accepted: November 21, 2015 Published: December 02, 2015
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.
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