title: Oroxylin A inhibits invasion and migration through suppressing ERK/GSK-3β signaling in snail-expressing non-small-cell lung cancer cells.
abstract: Snail is closely linked to tumor invasion, metastasis, and recurrence and indicates prognosis of patients suffering from cancer. Overexpression of Snail increases motility and invasiveness of cancer cells, which has become target for anti-metastatic treatment. Oroxylin A, a natural compound extracted from Scutellaria radix, has been reported to inhibit invasion and migration in breast cancer. In this study, we investigated the anti-invasive effect of oroxylin A on lung cells and uncovered its underlying mechanism. The results suggested that oroxylin A could inhibit migration and invasion in Snail-expressing 95-D, and A549 cells whereas it had little effect on non-expressing GLC-82 cells. Furthermore, enhanced Snail expression after transfection of Snail vector in GLC-82 cells is decreased by oroxylin A. Snail can also induce epithelial-mesenchymal transition. We found oroxylin A could reverse TGFβ1-induced epithelial-mesenchymal transition by inhibiting Snail expression. As a result, oroxylin A up-regulated E-cadherin expression and down-regulated vimentin, MMP-9, and CD44v6 expression, which could lead to the inhibition of tumor migration and invasion. Mechanically, we demonstrated that oroxylin A suppressed activation of ERK instead of AKT pathway and then promoted activation of GSK-3β to reduce Snail protein content. Finally, we established transplanted, metastatic, and orthotopic models of A549 cells, and found that oroxylin A inhibited the growth and lung metastasis of A549 cells in vivo. Taken together, we proposed that oroxylin A might be a promising candidate targeting tumor metastasis. © 2016 Wiley Periodicals, Inc.
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, P.R. China.
authors.forename: Libin
authors.initials: L
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, P.R. China.
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, P.R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, P.R. China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, P.R. China.
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Lu
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D000071679:Glycogen Synthase Kinase 3 beta
keywords: E-cadherin; ERK; GSK-3β; oroxylin A; snail