Ibuprofen and Sulindac Decrease T84 and PD Cell Proliferation and Affect Expression of the CFTR Promoter in Transfected PD Cells in vitro
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Cystic Fibrosis (CF) is an autosomal recessive disease caused by a malfunctioning CF channel, the cystic fibrosis transmembrane conductance regulator (CFTR). The non-steroidal anti-inflammatory drug (NSAID) ibuprofen has recently been shown to decrease symptom severity in CF patients. In this study the effects of two NSAIDs, ibuprofen and sulindac, on both CFTR promoter activity and cellular proliferation rates were examined in two epithelial cell lines, T84 and PD. After 3 days of incubation with either drug, a declining trend in cell proliferation rates was seen in both cell lines. Sulindac's effects were significant in both T84 and PD lines, but those of ibuprofen never reached statistical significance. Sulindac, after an initial decrease, increased promoter activity, as measured through a luciferase reporter assay, to over 150% control values. Ibuprofen steadily increased promoter expression to 250% control values after 7 days. These findings suggest that 1) ibuprofen may have a similar anti-proliferative effect to that previously noted with sulindac and 2) NSAIDs upregulate the CFTR promoter in transfected cells through an as yet undetermined mechanism.