Mengdan Li, Chen Wang, Jieyu Liu, Peiyu Jin, Fei Wang, Shengnan Liu, Shuhua Xi
Department of Environmental and Occupational Health, Liaoning Provincial Key Laboratory of Arsenic Biological Effect and Poisoning, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, 110122, People's Republic of China.
Environ Toxicol. 2017 Sep;32(9):2154-2162. doi: 10.1002/tox.22428. Epub 2017 Apr 26.
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.
流行病学研究表明，摄入无机砷会增加患膀胱癌的风险，慢性过度增殖可能在癌症发展中起直接作用。本研究考察了亚砷酸盐对JAK2/STAT3信号通路以及增殖和抗凋亡因子表达的影响。结果显示，长期低剂量接触亚砷酸盐可增强人尿道上皮细胞（SV-HUC-1细胞）的增殖能力，BrdU阳性率显著升高。随着接触时间的延长，慢性接触亚砷酸盐的SV-HUC-1细胞中增殖因子如细胞周期蛋白D1、COX-2和增殖细胞核抗原（PCNA）的mRNA和蛋白表达增加。此外，SV-HUC-1细胞接触亚砷酸盐后JAK2/STAT3信号通路被激活。敲低STAT3可降低亚砷酸盐诱导的细胞周期蛋白D1、COX-2、PCNA和BCL2的表达。总之，短期和长期接触亚砷酸盐后，砷可诱导人尿道上皮细胞增殖，JAK2/STAT3信号通路可能通过调节细胞周期蛋白D1、COX-2、PCNA和BCL2在亚砷酸盐诱导的增殖中起关键作用。
