Effects of angiotensinⅡtype 1 receptor antagonist in the inhibition of pancreatic cancer in vitro / 中华消化杂志

ABSTRACT

Objective To investigate the effects and mechanisms of selective angiotensinⅡtype 1 receptor antagonist ZD7155 on the inhibition of pancreatic cancer in vitro.Methods MTT assays were used to determine the inhibition of pancreatic cancer cell line PaTu8988s by ZD7155 in different concen- trations and at different time.PaTu8988s cell cycle and cell apoptosis were detected by flow cytometry. Transmission electron microscope was used to investigate the apoptosis of PaTu8988s before and after the incubation with ZD7155 under different concentrations.PaTu8988s cell morphology was observed be- fore and after the incubation with ZD7155.Results MTT showed that the increase of inhibition of pan- creatic cancer cell by ZD7155 was in agreement with the increase of the concentrations of ZD7155 and the time of the incubation with ZD7155.The inhibition rates of PaTu8988s cells were 9%,18%,30%, 51%,60% and 78% by ZD7155 with the concentrations of 5?10~(-11),5?10~(-10),5?10~(-9),5?10~(-8),5?10~(-7) and 5?10~(-6) mol/L,respectively.The inhibition rates of PaTu8988s cells were 15%,25%, 36%,51%,67% and 85% by ZD7155 with the same concentration(5.0?10~(-8) mol/L)at 12,24,36, 48,60 and 72 hours,respectively.ZD7155 could also inhibit PaTu8988s cell cycle significantly and was dose-dependent.Cell electron microscopy showed that there were chromatin margination and apoptotic body in the cell nucleus when the cells were incubated with ZD7155,and these changes were increase with the concentrations of ZD7155.The morphology of PaTu8988s cell didn't have any change after in- cubation with ZD7155.Conclusions ZD7155 can inhibit the growth of pancreatic cancer cells in vitro by suppressing the S-phase of cell cycle and induce cell apoptosis without visible cell toxic effects.