Low concentration arsenite activated JAK2/STAT3 signal and increased proliferative factor expressions in SV-HUC-1cells after short and long time treatment.

Abstract

Epidemiological studies have indicated that ingestion of inorganic arsenic resulted in increased risks of bladder cancer and chronic hyperproliferation could play a direct role in the development of cancer. This study examined the effects of arsenite on JAK2/STAT3 pathway and expressions of proliferation and anti-apoptosis factors. The results showed that long term exposure to low doses arsenite enhanced human uroepithelial cells (SV-HUC-1 cells) proliferation and BrdU positive rate was significant increased. mRNA and protein expressions of proliferation factors, such as cyclin D1, COX-2, and proliferating cell nuclear antigen (PCNA), increased in chronically exposed arsenite SV-HUC-1 cells with exposure time. Furthermore, JAK2/STAT3 signal pathway was activated following exposure to arsenite in SV-HUC-1 cells. Knockdown of STAT3 reduced expressions of cyclin D1, COX-2, PCNA, and BCL2 induced by arsenite. In conclusion, arsenic induced proliferation in human uroepithelial cells after short and long term exposure to arsenite and JAK2/STAT3 signaling pathway might be pivotal in arsenite-induced proliferation by regulating cyclin D1, COX-2, PCNA, and BCL2.