Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4.
Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4.
复制标题
DOI：
10.18632/oncotarget.6451
复制
发表时间：
2016-01-12
期刊：
影响因子：
--
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Tian L;Shen D;Li X;Shan X;Wang X;Yan Q;Liu J
上皮-间质转化（EMT）是肺癌转移的重要因素，靶向EMT是一种潜在的治疗策略。岩藻糖基转移酶IV（FUT 4）及其合成的癌糖抗原刘易斯Y（LeY）在许多癌症中异常升高。本研究以中药人参皂苷Rg 3为研究对象，探讨其抑制EMT和肺癌侵袭的糖生物学机制。我们发现Rg 3处理（25，50，100 μg/ml）通过伤口愈合和transwell实验抑制细胞的迁移和侵袭。Rg 3可显著改变EMT标志蛋白，增加E-cadherin表达，降低Snail、N-cadherin和Vimentin表达。qPCR、Western blot和免疫荧光检测结果显示Rg 3可下调肺癌细胞中FUT 4基因和蛋白的表达。shFUT 4下调FUT 4表达后，EMT明显受到抑制。此外，通过抑制LeY的生物合成抑制EGFR的活化，从而阻断下游MAPK和NF-κB信号通路。此外，Rg 3还能显著降低小鼠移植瘤的体积和重量，并能显著减少小鼠肺组织中的肿瘤转移结节。结论：Rg 3通过下调FUT 4介导的EGFR失活，阻断MAPK和NF-κB信号通路，抑制EMT和肺癌侵袭。Rg 3可能是一种潜在的有效的治疗肺癌的药物。
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.