The Effect And Mechanism Of Berberine Hydrochloride On Biological Function Of Esophageal Carcinoma Cell

BackgroundThe initial diagnoses of many esophageal cancer patients are made in an advanced stage of disease,making the surgery an undesirable option.Although advances in chemotherapy have been achieved,serious side effects usually limit clinical application.Exploring non-invasive strategies to prevent the growth of esophageal cancer is critically needed.Current research address that berberine is an inhibitor of human EC cell growth and could be considered as a potential source of drugs for the treatment of EC patients.ObjectiveTo study the effect of berberine on esophageal cancer(EC)cells and its molecular mechanisms.MethodsHuman esophageal squamous cell carcinoma(ESCC)cell line KYSE-70 and esophageal adenocarcinoma cell line SKGT4 were used.Transwell detect migration ability byesophageal squamous cell carcinoma(ESCC)cell line KYSE-70 The effect of berberine on cell proliferation was evaluated using3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.For cell cycle progression,KYSE-70 cells were stained with propidium iodide(PI)staining buffer(10 mg/mL PIand 100 mg/mL RNase A)for 30 min and cell cycle was analyzed using a BD FACSCalibur? Flow cytometer.For apoptosis assay,cells were stained with an Annexin V-FITC/PI Apoptosis Detection Kit according to the manufacturer's instructions.The rate of apoptotic cells was analyzed using a dual laser flow cytometer and estimated using the BD ModFit software.Levels of proteins related with cell cycle and apoptosis were examined by Western blot.ResultsBerberine treatment resulted in growth inhibition of both KYSE-70 and SKGT4 cells in a dose-dependent and time-dependent manner.KYSE-70 cells were relatively more susceptible to the inhibitory activities of berberine than SKGT4 cells.In KYSE-70 cells treated with 50 ?M berberine for 48 hours,cell population in cell cycle G2/M phase(25.94 ± 5.01%)was significantly higher than that in control group(9.77 ± 1.28%,P<0.01),and berberine treatment resulted in p21 upregulation in KYSE-70 cells.Flow cytometric analyses showed that berberine significantly augmented KYSE-70 apoptotic population at post-treatment 12 hours as well as 24 hours when compared with control cells(0.83% vs 43.78% at 12 hours,P<0.05;0.15% vs 81.86% at 24 hours,P<0.01),and berberine-induced apoptotic effect was stronger at 24 hours when comparing with incubation time for 12 hours.Western blot results showed that berberine inhibited the phosphorylation of Akt,mTOR and p70S6 K,enhanced AMPK phosphorylation in a sustained manner.ConclusionsBerberine is an inhibitor of human EC cell growth and could be considered as potential drug source for the treatment of EC patients.