ABSTRACT
Objective To discuss the influence of different concentration sulindac on pancreatic cancer cell line PANC-1 cell proliferation and apoptosis,and investigate the possible mechanism that sulindac can inhibit the Wnt/beta-catenin pathway to kill pancreatic cancer cells. Methods PANC-1 cell were divided into negative control group (added containing no sulindac DMSO)and experimental group (added sulindac with concentrations of 0.25 ,0.5 ,1 ,1.5 ,2 mM medium,respectively,name as 0.25 mM group,0.5 mM group,1.0 mM group,1.5 mM group,2.0 mM group),and treated with different time,cell proliferation inhibition ratio in each group was detected by MTT assay,cell apoptosis ratio was detected by flow cytometry,the expression ofβ-catenin mRNA and protein were detected by RT-PCR and immunocytochemistry.Results MTT results showed that sulindac can inhibit the cell proliferation of PANC-1 by a dose-and time-dependent manner.Cell apoptosis increased after sulindac treatment in different degrees,and there were statistical differences between 1.5,2.0 mMgroup and control groups (P<0.05).RT-PCR results showed that the expression ofβ-catenin mRNA decreased after the treatment of sulindac,there were statistical differences between 1.5,2.0 mMgroup and control group (P<0.05). In the 2.0mM group,the expression ofβ-catenin decreased along with the time extending (P<0.05 ).ICC results showed that sulindac inhibited the expression ofβ-catenin protein and nuclear accumulation,there were no statistical differences in 0.25 ,0.5 mM group and control group,but there were statistical differences in 1.0,1.5,2.0 mMgroup.Conclusion Sulindac could inhibit cell proliferation and facilitate apoptosis of PANC-1,this effect is dose-and time-dependent.The inhibition of Wnt/beta-catenin signal pathway may be a possible mechanism of its cytotoxicity.