CN: 32-1845/R
ISSN: 2095-6975
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FENG Hai-Tao, ZHAO Wen-Wen, LU Jin-Jian, WANG Yi-Tao, CHEN Xiu-Ping. Hypaconitine inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses adhesion,migration,and invasion of lung cancer A549 cells[J]. Chinese Journal of Natural Medicines, 2017, 15(6): 427-435

Hypaconitine inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses adhesion,migration,and invasion of lung cancer A549 cells

FENG Hai-Tao, ZHAO Wen-Wen, LU Jin-Jian, WANG Yi-Tao, CHEN Xiu-Ping
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
Abstract:
Epithelial-mesenchymal transition (EMT) has been implicated in tumor invasion and metastasis and provides novel strategies for cancer therapy. Hypaconitine (HpA), a diester-diterpenoid alkaloid isolated from the root of the Aconitum species, exhib-its anti-inflammatory, analgesic, and especially, cardiotoxic activities. Here, we reported the anti-metastatic potentials of HpA in trans-forming growth factor-β1 (TGF-β1)-induced EMT in lung cancer A549 cells. The cytotoxic effect of HpA was determined by MTT assay. A549 cells were treated with TGF-β1 with or without HpA co-treatment, and the morphological alterations were observed with a microscopy. The expression of E-cadherin, N-cadherin, and NF-κB was determined by both Western blotting and immunofluorescence analy-ses. The adhesion, migration, and invasion were detected with Matrigel, wound-healing, and transwell assays, respectively. The expres-sion of Snail was determined by Western blotting. The expression of NF-κB p65, IκBα, and p-IκBα in nuclear and cytosolic extracts was assessed by Western blotting. The results showed that low concentration of HpA (<16μmol L–1) had no obvious cytotoxicity to A549 cells. Morphologically, TGF-β1 treatment induced spindle-shaped alteration in the cells. The upregulation of N-cadherin, NF-κB, and Snail and the downregulation of E-cadherin were detected after TGF-β1 treatment. The adhesion, migration and invasion abilities were also increased by TGF-β1. Besides, TGF-β1 induced expression of Snail in a time-dependent manner. Furthermore, TGF-β1 induced nuclear translocation of NF-κB p65. All these alterations were dramatically inhibited by HpA co-treatment. In addition, the NF-κB inhibitor PDTC showed similar inhibitory effect. In conclusion, these results showed that HpA inhibited TGF-β1-induced EMT in A549 cells, which was possibly mediated by the inactivation of the NF-κB signaling pathway, providing an evidence for anti-cancer effect of HpA.
Key words:    EMT    Hypaconitine    TGF-β1    NF-κB   
Received: 2016-12-21   Revised:
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