Effect of low concentrations of p,p′- dichlorodipheny ltrichloroethane on proliferation and apoptosis of coIorectal adenocarcinoma SW620 cells / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the effect and mechanism of low concentrations of p,p′-dichlorodiphenyltrichloroethane (p,p′-DDT) on colorectal adenocarcinoma SW620 cell proliferation and apoptosis. METHODS SW620 cells were exposed to low concentrations of p, p′-DDT ranging from 1×10-12 to 1×10-6 mol.L-1 for 48 and 96 h. MTT assay was employed to examine the effect of p,p′-DDT on SW620 cell viability. Different cell stages of cycle and apoptosis rate were determined by flow cytometry after SW620 cells were exposed to 1×10-10 , 1×10-9 and 1×10-8 mol.L-1 for 96 h. Western blotting was used to determine the protein expression of Wnt/ β-catenin signaling components 〔β-catenin, phospho-β-catenin and phospho-glycogen synthase kinase ( GSK) 3β〕, their downstream target proteins ( c-Myc and cyclin D1)and apoptosis related proteins (Bcl-2, Bax, procaspase 8 and procaspase 3). RESULTS The viability of colorectal adenocarcinoma SW620 cells was significantly increased after exposure to low concentrations of p,p′-DDT ranging from 1×10-12 to 1×10-7 mol.L-1 for 96 h. p,p′-DDT 1×10-10 , 1×10-9 and 1×10-8 mol.L-1 exposure led to a decreased percentage of SW620 cells in G1 stage(P<0.01) along with an increased percentage of cells in S stage(P<0.01). Meanwhile, the apoptosis rate was signifi-cantly decreased compared with control group ( P < 0. 01). Exposure to p, p′-DDT from 1 × 10-10 to 1×10-8 mol.L-1 induced upregulation of phospho-GSK3β ( Ser9), β-catenin, c-Myc and cyclin D1 in SW620 cells( P <0.01). Moreover, apoptosis related proteins Bcl-2, procaspase 8 and procaspase 3 were unregulated(P<0.01), and Bax level and caspase 3 activity were decreased in p,p′-DDT-stimulated cells(P < 0.01). CONCLUSION Low concentrations of p, p′-DDT exposure activates Wnt/ β-catenin signaling and affects apoptosis-related proteins, which may be involved in p,p′-DDT-induced cell prolifer-ation as well as suppression of cell apoptosis in SW620 cells.