Short hairpin RNA targeting β-catenin suppresses cell proliferation and induces apoptosis in human gastric carcinoma cells

Abstract Objective. Aberrant activation of Wnt/β-catenin signaling is involved in various cancers, including human gastric cancer. Here we investigate the role of Wnt/β-catenin signaling in regulating gastric cancer cell apoptosis. Material and methods. Expression of β-catenin was investigated after transfection with β-catenin short hairpin RNA (shRNA) in gastric cancer cells by Western blotting and immunofluorescence analysis. β-catenin/T-cell factor transcriptional activity was also investigated by using a luciferase reporter assay. Next, the effects of β-catenin shRNA on cell proliferation and apoptosis were evaluated by the 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide assay and flow cytometric analysis. To investigate the precise mechanism of these effects, a comprehensive analysis was performed using a cDNA microarray. Results. shRNA targeting β-catenin resulted in a significant decrease in β-catenin expression, and its nuclear localization and cell proliferation. Meanwhile, increased cell apoptosis was confirmed. The comprehensive analysis showed that shRNA targeting β-catenin upregulated 26 apoptosis-related genes (including PERP, TRAF3, PDCD2, TNFRSF25, AKT2 and YWHAZ) and downregulated 48 apoptosis-related genes (including MALT1, IRAK1, TNFAIP3, PPP1R13L, TRIP and YWHAB) in gastric cancer cells. Pathway analysis suggested that the nuclear factor-kappaB pathway was involved in β-catenin knockdown-induced apoptosis. Conclusions. Attenuation of β-catenin by shRNA resulted in suppressed cell proliferation and apparent apoptosis, suggesting that β-catenin may be a target for therapy of gastric cancer.