Arsenic trioxide inhibits the growth of human gall bladder carcinoma cell and its effect on the cyclin D1 / 中国癌症杂志

ABSTRACT

Background and purpose:Arsenic trioxide,verified as a breakthrough in the management of acute promyelocytic leukemia,has been applied to a variety of solid tumors.Gall bladder carcinoma,lacking specific clinical manifestations,is usually diagnosed at advanced stages of the diseases and few cases can be resected by operation.Chemotherapy has not shown significant activity in gall bladder carcinoma.This study was to investigate the biological effect of As2O3 on the growth of human gall bladder carcinoma cell and its mechanism.Methods:GBC cells were cultured with different concentrations of As2O3,the proliferative activity of the cells was detected by MTT methods,and the cell cycle status was carried out by flow cytometry(FCM).Western blot and RT-PCR were performed to analyse the expression of cyclin D1,D2,D3,CDK4 and CDK6.GBC cells were transient transfected with cyclin D1 promoter construct pGL3 and then treated by different doses of As2O3.The luciferase activity was measured.Results:The treatment of As2O3 in gall bladder carcinoma cells could inhibit the growth of cells in a time and dose dependent manner,make cells arrest in G1 phase and down regulate the expression of cyclin D1.In addition,the activity of cyclin D1 promoter was down-regulated by As2O3 in a dose-dependent manner and decreased about 70 percent when treated with 4 ?mol/L As2O3.Conclusions:As2O3 can significantly inhibit the growth of human gall bladder carcinoma cells as well as down-regulate the expression of cyclin D1 in vitro.