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Vitamin D favorably alters the cancer promoting prostaglandin cascade.

BACKGROUND
Preclinical studies suggest that 1,25-dihydroxyvitamin D [1,25(OH)2D] and celecoxib inhibit prostaglandins (PGs) associated with cancer through different mechanisms. We determined if there was synergy in their use.


PATIENTS AND METHODS
A total of 36 healthy women received daily for one month/menstrual cycle: placebo, 400 international units (IU) vitamin D-3, 2,000 IU vitamin D-3, or 2,000 IU vitamin D-3 plus 400 mg celecoxib. Serum and nipple aspirate fluid (NAF) were analyzed for PGE2 and transforming growth factor (TGF)β1 and -2; serum for 25(OH)D (total, -D-2, -D-3), plasma for celecoxib; and mammary duct RNA for cyclooxygenase (COX)2.


RESULTS
25(OH)D-3 increased (p<0.01) only in the groups receiving 2,000 IU vitamin D-3. PGE2 decreased in the breast (p=0.01) only after receiving 2,000 IU vitamin D-3; 2,000 IU vitamin D-3 alone was more effective in decreasing PGE2 than 2,000 IU vitamin D-3 plus celecoxib (p=0.018). COX2 expression decreased only in the breasts of women taking 2,000 IU vitamin D-3. Change in circulating 25(OH)D-3 correlated with change in TGFβ2 in the breast.


CONCLUSION
Vitamin D-3 reduces the PG cascade and increases TGFβ2 in a dose-dependent fashion. Adding celecoxib did not provide synergy.