Effects Of Polychlorinated Biphenyl 118 On Proliferation And Apoptosis Of The Rat Insuloma INS-1 Cells

Objective To observe the effect of environmental endocrine disruptors polychlorinated biphenyl 118(PCB-118)on proliferatin and apoptosis of rat insuloma INS-1 Cells and its mechanism.Methods INS-1 cells were cultured with different concentrations(0,10,20,30,40,50,60,70,80,90 ?M)of PCB-118,and the vability of cells was measured by MTT assay.Apoptosis of INS-1 cells treated by PCB-118 was detected by Annexin V-PI double staining flow cytometry(FCM).After treated with PCB-118 for 72 h,the expression of Bax and Bcl-2 proteins in INS-1 cells was detected by Western blot.Quantitative PCR was used to detect the mRNA expression of Insulin1,Insulin2,pancreatic duodenal homeobox factor-l(Pdx1)and Glucose transporter 2(Glut2)in INS-1 cells after treated with PCB-118 for 72 h.Results The MTT assay showed that the proliferation of INS-1 cells was significantly inhibited from 20 ?M PCB-118 group after it was treated for 72 h.The FCM showed that the apoptosis rate of INS-1 cells was increased after treated with 10 ?M and 50 ?M PCB-118 for 72 h,and the apoptosis rate in 50 ?M PCB-118 group increased more significantly(P<0.05).Furthermore,after treated with PCB-118 for 72 h,the expression of Bax protein increased while Bcl-2 protein decreased,and the Bcl-2/Bax ratio was significantly decreased(P<0.01 or P<0.001).The mRNA expression of Insulin1, Insulin2,Pdx1 and Glut2 decreased in dose-dependent manner after treated by PCB-118(P<0.05 or P<0.01).Conclusion Environmental endocrine disruptor PCB-118 has the patential to inhibit the proliferation of rat pancreatic beta cell INS-1,induce its apoptosis,and decrease the expression of ?-cell function-related genes.These results suggested a possible mechanism of PCB-118 in the pathogenesis of diabetes.