Effects Of Berberine On Proliferation, Migration And Invasion Of A549Lung Adenocarcinoma Cells

BackgroundLung cancer is one of the leading causes of cancer-related deaths worldwide andnon-small cell lung cancer (NSCLC) accounts for about75%~85%of all lung cancers.NSCLC often presents at stages too late for surgical intervention and traditional treatmentsincluding chemotherapy and radiotherapy are inadequate. The response rate of first-linechemotherapy ranges from20%~40%, and the median overall survival of NSCLC patientsare8~10months. The existing chemotherapy regimens have reached a platform.Findsafe,effective, low toxicity of anticancer drugs from natural compounds, has become animportant development strategy.Berberine is extracted from plants monomeric isoquinolinealkaloids, a large number research has demonstrated its anti-tumor activity. But thepotential role and underlying mechanisms that BBR inhibit the proliferation and metastasisof lung cancer has not been reported.Recent studies have shown thatepithelial-mesenchymal transition plays a pivotal role in cancer progression.In our study,we attempted to investigate the regulation of BBR for EMT-associated proteins.PurposeTo observe the effects of BBR on the proliferation and apoptosis of humanadenocarcinoma A549cells,assess the expression levels of EMT-relevant proteins after thetreatment of BBR and to explore their possible mechanisms.Methods1. The A549cells was treated with BBR at different concentrations in different times.The inhibitory rates of cell proliferation was assessed byMTT.2. After treatment with different concentrations BBR, the apoptosis of A549cells wasanalyzed by folw cytometry (FCM).3. After treatment with different concentrations BBR, the inhibition of migration andinvasion was evaluated by transwell assay.4. The expression levels of EMT maker in A549cells were examined by Western blotting.5. The expression levels of EMT-relevant transcription factors in A549cells were alsoexamined by Western blotting.Results1. The proliferation of A549cells was inhibited via treatment with differentconcentrations of BBR in a dose-and time-dependent manner (P＜0.05).2.BBR can induce A549cell apoptosis. The apoptotic rates of A549cells wassignificantly increased in BBR treated groups compared with those in the control group (P＜0.05).3.BBR can inhibited the migration and invasion of A549cell compared with controlgroup in a dose-dependent manner (P＜0.05).4.BBR increased the expression of the epithelial phenotype marker E-cadherin,repressed the esenchymal phenotype marker Vimentin.5. BBR decreased the levels of epithelial-to-mesenchymal-inducing transcriptionfactors Snail1and Slug.Conclusions1. BBR can inhibit the proliferation of human NSCLC A549cells and induce theirapoptosis.2. BBR may inhibited the migration and invasion of A549cell through the regulationofEMT-related genes expressionand their possible mechanisms needed further study.