BASIC BIOLOGY

recent studies had shown that the long-term use of high concentration of COX-2 inhibitors may be limited due to evidence of an elevated risk of cardiovascular complications. Rosiglitazone (RGZ) is a new class of oral anti-diabetic drug that have been shown to inhibit growth of some epithelial cancer cells. In this study we investigated whether RGZ potentiates the growth inhibition effect of a specific COX-2 inhibitor (NS-398) in a human pancreatic cancer cell line, SW1990. Methods SW1990 cells were routinely cultured in DMEM supplemented with 10% fetal calf serum. Subconfluent cell cultures were treated with either RGZ (6.25–100 μmol/L), or NS-398 (25–200 μmol/L), or RGZ (50μmol/L) in combination with NS-398 (150 μmol/L) for 12, 24 and 48 h. The cell viability was determined by MTT assay and proliferating cell nuclear antigen (PCNA) was detected using immunocytochemistry. Flow cytometric analysis was used to detect the apoptosis. The expression of apoptosis-inhibited gene bcl-2 was assessed by RT-PCR. Results RGZ and NS-398 significantly inhibited SW1990 cell viability in a dose and time dependent manner. The survival rate in the cells treated with both of RGZ and NS-398 was much lower than that with the two agents applied alone (P < 0.01). The expression rate of PCNA significantly decreased in the cells after treatment with either RGZ or NS-398 (P < 0.01). Apoptosis rate was (14.51 ± 0.36)%, (10.65 ± 3.93)% and (25.87 ± 5.24)% in the cells treated with RGZ, NS-398, and the combination of two agents respectively, which was significantly higher than that in the control group (P < 0.05). RGZ and NS-398 significantly reduced the expression of bcl-2 mRNA in SW1990 cells (P < 0.05). Conclusions RGZ synergistically increases anticancer role which was associated with the proliferation inhibitory and pro-apoptotic effects of NS-398 in pancreatic cancer cells. The synergistic effect may enable the use of specific COX-2 inhibitor at lower and safer concentrations for treatment in human pancreatic cancer.