Epithelial-to-mesenchymal transition markers to predict response of Berberine in suppressing lung cancer invasion and metastasis.
BACKGROUND
The effects of berberine on the metastatic potential of lung cancer cells and its underlying mechanisms have not been fully elucidated. Since epithelial-to-mesenchymal transition is a cellular process associated with cancer invasion and metastasis, we attempted to investigate the potential use of berberine as an inhibitor of TGF-β1-induced epithelial-to-mesenchymal in A549 cells.


METHODS
In this study, we investigated the anticancer activity of berberine against A549 cells in vitro and in vivo. BBR-induced apoptosis of the human lung cancer cells was determined by flow cytometry. The ability of BBR to inhibit TGF-β-induced EMT was examined by QRT-PCR and Western blotting. The impact of BBR on A549 cell migration and invasion was evaluated by transwell assay.


RESULTS
We demonstrated that TGF-β1 induced epithelial-to-mesenchymal to promote lung cancer invasion and metastasis. Berberine inhibited invasion and migration of A549 cells, increased expression of the epithelial phenotype marker E-cadherin, repressed the expression of the mesenchymal phenotype marker Vimentin, as well as decreased the level of epithelial-to-mesenchymal -inducing transcription factors Snail1 and Slug during the initiation of TGF-β1-induced epithelial-to-mesenchymal. Furthermore, berberine inhibited growth of lung cancer cells in vivo xenograft.


CONCLUSIONS
Our findings provided new evidence that berberine is an effective inhibitor of the metastatic potential of A549 cells through suppression of TGF-β1-induced epithelial-to-mesenchymal.
Hui-wei
HW
Qi
Ling-yan
LY
Xin
Xin
X
Xu
Xian-xiu
XX
Ji
Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, PR China. fanlih@aliyun.com.
Li-hong
LH
Fan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001599:Berberine / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D001599:Berberine; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9