Effects Of Specific COX-2 Inhibitor And PPARγ Agonist On Proliferation And Apoptosis In Pancreatic Cancer

Objective: Cyclooxygenase-2 (COX-2) and peroxisome proliferators-activated receptor-gamma(PPARγ) play very important roles in occurrence, progression and prognosis of tumor. But the definite effects and mechanisms of specific COX-2 inhabitor and PPARγagonist on the prevention and cure of pancreatic cancer have not been fully elucidated. The present study investigated the effects of a specific COX-2 inhabitor(NS-398) and a selected PPARγagonist(rosiglitazone) on the proliferation and apoptosis of pancreatic cancer SW1990 cell line to examine whether the two non-celltoxicity agents have synergistic anticancer role, so as to establish the experimental bases for application PPARγagonist associating with specific COX-2 inhabitor in treating pancreatic cancer.Methods: SW1990 cells were incubated in the medium with NS-398[(25,50,100,150,200)μmol/L], rosiglitazone[(6.25,12.5,25,50,100)μmol/L] and the combination of these two agents(150μmol/L NS-398 and 50μmol/L rosiglitazone), respectively. Cell growth and proliferation of SW1990 cells were analyzed with MTT assay; expression of proliferating cell nuclear antigen(PCNA) protein in SW1990 cells was detected by immunocytochemistry; apoptosis was detected with flow cytometry assay; expression of bcl-2 mRNA was determined by RT-PCR.Results: Both of NS-398 and rosiglitazone inhibited SW1990 cell proliferation in a time and dose dependent manner. Combination with NS-398 and rosiglitazone inhibited the proliferation more remarkably than the two agents applied alone (P<0.01). NS-398 and rosiglitazone markedly decreased PCNA expression in SW1990 cells (P < 0.01). Apoptosis rates were (10.65±3.93)%, (14.51±0.36)% and ( 25.87±5.24)% in SW1990 cells treated with NS-398, rosiglitazone and combination of the two agents, respectively, which were significantly higher than that in the control group[(3.12±1.76)%, P<0.05 or P<0.01]. The apoptosis rates in the cells treated with NS-398 and rosiglitazone were was much greater than that treated with NS-398 or rosiglitazone applied singly(P<0.01). NS-398 and rosiglitazone down-regulated bcl-2 mRNA expression respectively (P<0.01); expression of bcl-2 mRNA in the cells treated with NS-398 and rosiglitazone was much lower than that with the two agents applied singly(P<0.05).