P5-07-02: Could the Combination of COX-2 Inhibitor and Calcitriol Be a New Chemopreventive Approach To Decrease the Incidence of Breast Cancer?

Abstract

Abstract Background COX-2 is a potential molecular prognostic factor for breast cancer and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is described as a tumour suppressor in cancer. The antiproliferative effects of calcitriol (1,25(OH)2D3) mediated via the vitamin D receptor (VDR) render vitamin D a promising target in breast cancer therapy. Material and Methods: The expression of the prostaglandin (PG) metabolising enzymes (COX-2, 15-PGDH), the PG receptors, the vitamin D metabolising enzymes (1-alpha-hydroxylase, 24-hydroxylase) and the VDR were determined in benign and malignant breast cell lines as well as in normal and malignant breast tissue. Measurement of PGE2 and 25(OH)2D3 serum level in healthy women and breast cancer patients was performed in winter and summertime. Additionally, the influence of calcitriol on cell proliferation was determined. In addition we examined the effect of calcitriol on the enzyme expression. Results: We found an inverse correlation between the expression of the PG metabolising enzymes with the VDR as well as with the vitamin D metabolising enzymes by investigating the tissue samples. Moreover, we detected an inverse correlation between the PGE2 and 25(OH)2D3 serum level in breast cancer patients during wintertime. Furthermore the PG receptors were associated with an increased carcinogenesis. The breast cell experiments presented a dysregulated vitamin D metabolism, especially in the invasive breast cell line. Calcitriol showed an antiproliferative effect only in the benign but not in the malignant cell lines, and the expression of COX-2 and 15-hydroxyprostaglandindehydrogenase was influenced by calcitriol only in the benign breast cell line. Conclusions: These results suggest a link between vitamin D and PG metabolism and therefore a possible synergism between COX-2 inhibition and calcitriol in breast cancer cells. For the first time, we could show an inverse correlation between the two metabolisms in breast cancer on different levels. Thus, the chemopreventive combination of calcitriol and/or vitamin D analogue with a COX-2 inhibitor might decrease the incidence of breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-07-02.