Effects and mechanisms of action of SARI on androgen-independent prostate cancer (DU145) cells.

ABSTRACT

This study aimed to characterize the role and mechanisms of action of suppressor of AP-1, regulated by IFN (SARI) in androgen-independent prostate cancer cells using the DU145 cell line. Prostate cancer cell lines were transfected to permit both the overexpression and inhibition of SARI. MTT assays and Transwell assays were performed to detect the effects of SARI overexpression and inhibition on the proliferation activity, invasiveness, and metastatic ability of DU145 cells. Expression of vascular endothelial growth factor (VEGF) and tyrosine-phosphorylated signal transducer and activator of transcription 3 (p-STAT3) was monitored in the experimental groups using a qPCR assay and western blot analysis. Additionally, DU145 cells were separately treated with 5, 50, and 100 µmol/L AG490 for 48 h and SARI expression was detected using the qPCR assay and western blot analysis. We also monitored the effects of AG490 treatment (100 µmol/L for 48 h) on both the SARI-SiRNA DU145 cells and empty vector DU145 (DU145-V) cells using the MTT assay and a Transwell migration assay. SARI overexpression and SARI-SiRNA DU145 prostate cancer cell lines were successfully established. The proliferation activity and the invasion and migration abilities of DU145-SARI cells were significantly lower compared with the DU145-V group (P < 0.05). Conversely, the proliferation activity and the invasion and migration abilities of SARI-SiRNA cells were significantly higher compared with the DU145-V group (P < 0.05). VEGF and p-STAT3 expression levels were lower in the SARI overexpression group compared with the DU145-V group and the control group (P < 0.05). In contrast, VEGF and p-STAT3 expression levels were higher in the SARI-SiRNA group compared with both the DU145-V group and the control group (P < 0.05). In comparison with the control group, SARI expression levels were higher in DU145 cells treated with 50 and 100 µmol/L AG490. Upon treatment with 100 µmol/L AG490 for 48 h, the proliferation activity and invasiveness and migration abilities of SARI-SiRNA cells were significantly higher compared with the DU145-V group (P < 0.05). SARI significantly affects the proliferation, invasion, and metastasis of DU145 cells. It is possible that SARI inhibits the proliferation, invasion, and migration of androgen-independent prostate cancer cells by regulating downstream genes through the SARI/STAT3/VEGF pathways.