ABSTRACT
OBJECTIVE@#To explore the eff ect of grape seed proanthocyanidins extract (GSPE) on the growth of pancreatic cancer cells and the underlying mechanisms.@*METHODS@#The pancreatic cancer AsPC-1 cells were cultured in vitro. The effects of GSPE on cell proliferation, apoptosis and migration were analyzed by MTT, Annexin V-FITC/PI and Transwell migration assay, respectively. The expression of miR-27a and FOXO1 in AsPC-1 cells was determined by real-time RT-PCR and Western blot, respectively. The miR-27a inhibitors were applied to verify the role of miR-27a in mediation of GSPE effects.@*RESULTS@#GSPE inhibited cell growth in a dose-dependent manner. This inhibitory effect was significant when the dosage of GSPE was more than 50 μg/mL (P<0.05 vs control). GSPE also could induce apoptosis and inhibit cell migration. MiR-27a expression was notably down-regulated when the dosage of GSPE was 75 μg/mL (P<0.01 vs control). Compared with the control group, cell proliferation inhibition was significantly increased in the miR-27a inhibitor group, the GSPE group and the miR-27a inhibitor plus GSPE group (P<0.01), while cell migration was significantly decreased (P<0.01). Compared with the GSPE or the miR-27a inhibitor group, the growth and migration inhibitory effects in the miR-27a inhibitor plus GSPE group were more obviously (P<0.01). Both GSPE and miR-27a inhibitor alone could up-regulate FOXO1 expression. But these effects were more apparent when they are applied in combination.@*CONCLUSION@#GSPE inhibites AsPC-1 cells' growth and migration partly through down-regulation of miR-27a expression.
Subject(s)
Humans , Apoptosis , Cell Line, Tumor , Cell Movement , Cell Proliferation , Down-Regulation , Grape Seed Extract , Pharmacology , MicroRNAs , Genetics , Metabolism , Pancreatic Neoplasms , Pathology , Proanthocyanidins , Pharmacology , Up-RegulationABSTRACT
<p><b>OBJECTIVE</b>To ascertain whether proanthocyanidins inhibit cell growth and migration by increasing let-7a expression in pancreatic cancer AsPC-1 cells.</p><p><b>METHODS</b>The proliferation rate, cell apoptosis rate and cell migration ability of AsPC-1 cells treated with proanthocyanidins were measured by MTT assay, Annexin V-FITC/PI staining, and Transwell migration assay, respectively. The expression of let-7a AsPC cells was detected by miRNA real-time RT-PCR after proanthocyanidins treatment. The changes in the biological behaviors of AsPC-1 cells were evaluated after transfection with let-7a mimics.</p><p><b>RESULTS</b>Compared with the control group, proanthocyanidins treatment caused dose-dependent decrements of the proliferation rate and migration ability and increased the apoptosis rate in AsPC-1 cells. AsPC-1 cells with proanthocyanidins treatment showed increased expression of let-7a. Transfection with let-7a mimics resulted in obvious decreases in the cell growth rate and migration ability, and proanthocyanidins treatment significantly enhanced the inhibitory effect of let-7a mimics.</p><p><b>CONCLUSION</b>Proanthocyanidins-induced cell growth and migration inhibition are partially mediated by up-regulation of let-7a expression in AsPC-1 cells.</p>