Article Figures & Data
Figures
- Fig. 1.
Effects of NSAIDs on the expression of PSA and hK2 proteins in prostate cancer cells ± 1 nm Mib. LNCaP cells (A) and LAPC-4 cells (B) were treated with or without the indicated concentrations of celecoxib and nimesulide for 7 days. Spent media were collected and used for PSA (Hybritech) or hK2 (sandwich) immunoassay. PSA and hK2 values were normalized to growth response measured by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and expressed as a percentage of that of groups treated with Mib only. Error bars indicate the SE of four separate experiments.
- Fig. 2.
A, effects of NSAIDs on the expression of AR protein and FKBP51 in LNCaP cells by Western blot analysis. B, LNCaP cells were transfected with a luciferase reporter plasmid containing the 6-kb PSA promoter or three copies of ARE or control plasmid (pGL3) and a CMV-β-gal expression vector and treated with NSAIDs ± 1 nm Mib for 24 h. ∗, P < 0.05 for PSA promoter and hK2–3ARE promoter. After normalization with β-gal, luciferase activities were expressed as a percentage of that of groups treated with Mib only. C, effects of NSAIDs on the expression of c-Jun and phospho-c-Jun (p-c-Jun) in LNCaP cells by Western blot analysis. Whole cell lysates were prepared from cells treated with or without celecoxib and nimesulide at the indicated concentrations for 15 or 24 h. β-Tubulin was used as an internal control for protein loading and transfer efficiency in A and C.
- Fig. 3.
A, LNCaP cells were cotransfected with AR promoter-luciferase reporter (AR-pGL3) or the parental vector (pGL3) and CMV-β-gal and treated with 1 nm Mib and NSAIDs at the indicated concentrations for 24 h. B, LNCaP cells were cotransfected with AR promoter (−74/+87)-pGL3, AR promoter (−1380/+577)-pGL3, or the parental vector (pGL3) plus CMV-β-gal and different amounts of c-jun expression vector for 24 h. Cell extracts were prepared from the above-mentioned transfections for luciferase and β-gal assays. The resulting activities of both AR-pGL3 were further normalized to β-gal and expressed as a percentage of the AR promoter (−1380/+577) without NSAIDs or c-jun. ∗, P < 0.05 for AR promoter (−1380/+577)-pGL3; ∗∗, P < 0.05 for AR promoter (−74/+87)-pGL3.
Tables
- Table 1
Effects of selected NSAIDs on growth responses and expression of androgen-regulated genes in androgen-responsive human prostate cancer cell lines
NSAIDs Selective inhibitor to LNCaP (IC50)a LAPC-4 (IC50)a Growth PSA hK2 Growth PSA hK2 Aspirin COX-1 and -2 >1000 >1000 >1000 >1000 >1000 >1000 Ibuprofen COX-1 and -2 >1000 783.3 860 740 870 803 Meloxicam COX 2 193.1 300 377 92 >300 >300 Ketoprofen COX-1 and -2 >300 >300 >300 >300 >300 >300 Flurbiprofen COX-1 and -2 >300 206 281 347 234 221 Nimesulide COX-2 38.2 27 23 104 76.5 61 Sulindac COX-1 and -2 >300 >300 >300 >300 >300 >300 Sulindac sulfone b >300 206 97.6 253 193.8 >300 Celecoxib COX-2 32.6 20 29.6 44.5 28.7 43.7 Fenoprofen COX-1 and -2 >300 210.4 228.6 N/Dc N/D N/D Indomethacin COX-1 and -2 >300 224 272 170 203 207 -
a IC50 is given in μm.
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b A metabolite of sulindac loses NSAID activities.
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c N/D, not determined.
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Volume 12, Issue 8
