N-myc downstream regulated gene 2 promotes apoptosis of bladder cancer cells through signal transducer and activator of transcription 3 signaling pathway

Abstract

Objective To investigate the effect of N-myc downstream regulated gene 2(NDRG2) on the apoptosis of bladder cancer cells by regulating the signal transducer and activator of transcription 3(STAT3) signaling pathway. Methods The expression level of NDRG2 in human bladder cancer cell BIU-87 and immortalized cell SV-HUC-1 was detected by Western blot. NDRG2 over expression vector and empty vector control (pcDNA3.1), siRNA-NDRG2, siRNA control were transfected into BIU-87 cells.After transfected 48 h, the expression level of NDRG2, Cleaved caspase 3, STAT3, p-STAT3, JAK2, p-JAK2 were detected by Western blot , the cell proliferation and apoptosis were measured by MTT and flow cytometry. After adding inhibitor AG490 of 45 μmol/L in cultured BIU-87 cells, MTT assay was used to detect cell proliferation and flow cytometry was used to detect the cell apoptosis, Western blot to detect the expression level of Cleaved caspase 3, STAT3, p-STAT3, JAK2, p-JAK2. Results The expression level of NDRG2 in bladder cancer cells was higher than that in bladder epithelial cells. The cell survival rate of pcDNA3.1/NDRG2 group was lower than that of pcDNA3.1 group, the difference was statistically significant (P<0.01). The cell survival rate of siRNA-NDRG2 group was higher than that of siRNA control group (P<0.01). The apoptosis rate of pcDNA3.1/NDRG2 group was higher than that of pcDNA3.1 group (P<0.01). The apoptosis rate of NDRG2 siRNA group was lower than that of siRNA control group (P<0.01). The level of p-STAT3 and p-JAK2 in pcDNA3.1/NDRG2 group was lower than that in pcDNA3.1 group (P<0.01). The survival rate and apoptosis rate of BIU-87 cells cultured with AG490 were in agreement with the trend of pcDNA3.1/NDRG2 after transfection. Conclusions NDRG2 could promote the apoptosis of bladder cancer cells, and its mechanism may be related to STAT3 signaling pathway. Key words: Bladder neoplasms; N-myc downstream regulated gene 2; Signal transducer and activator of transcription 3; Apoptosis