1,25-Dihydroxyvitamin D3 inhibits growth of the breast cancer cell line MCF-7 and downregulates cytochrome P4501B1 through the COX-2/PGE2 pathway

  • Authors:
    • Lei Yuan
    • Rong Jiang
    • Yingχue Yang
    • Songtao Ding
    • Huayu Deng
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  • Published online on: September 12, 2012     https://doi.org/10.3892/or.2012.2031
  • Pages: 2131-2137
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Abstract

Cytochrome P4501B1 (CYP1B1) is responsible for tumor progression in estrogen receptor-positive breast cancer due to its key role in estrogen metabolism, which is upregulated by PGE2, the main product of COX-2 that is found to be overexpressed in many breast tumors. Previous studies reported that inhibition of the COX-2/PGE2 pathway, by 1,25-dihydroxyvitamin D3 in MCF-7 breast cancer cells. The aim of this study was to investigate if the CYP1B1 protein expression shows covariation with the COX-2 and phosphorylated ERα (p-ERα) in human breast cancer. We also investigated whether 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] downregulates CYP1B1 via the COX-2/PGE2 pathway in MCF-7 cells. We analyzed the expression of COX-2, p-ERα and CYP1B1 using an immunohistochemical staining assay. In the present study, COX-2 was correlated to p-ERα (P<0.001) and CYP1B1 (P=0.001), p-ERα was correlated to CYP1B1 (P=0.012). We assessed the effects of 1,25(OH)2D3 on MCF-7 cells. 1,25(OH)2D3 treatment inhibited MCF-7 cell growth in a time-and dose-dependent manner; the cell cycle was arrested in the G0/G1 phase. Treatment with 100 nmol/l 1,25(OH)2D3 for 72 h significantly decreased the expression of COX-2 mRNA in MCF-7 cells (P<0.05), decreased the levels of PGE2 in cell culture supernatant (P<0.01), and downregul­ated p-ERK, p-ERα and CYP1B1 protein expression (P<0.05). Taken together, these results suggest that the COX-2/PGE2 pathway positively regulates the expression of CYP1B1 in breast cancer. 1,25-Dihydroxyvitamin D3 inhibits the growth of MCF-7 cells and downregulates CYP1B1 mediated by the COX-2/PGE2 pathway.
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December 2012
Volume 28 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yuan L, Jiang R, Yang Y, Ding S and Deng H: 1,25-Dihydroxyvitamin D3 inhibits growth of the breast cancer cell line MCF-7 and downregulates cytochrome P4501B1 through the COX-2/PGE2 pathway. Oncol Rep 28: 2131-2137, 2012
APA
Yuan, L., Jiang, R., Yang, Y., Ding, S., & Deng, H. (2012). 1,25-Dihydroxyvitamin D3 inhibits growth of the breast cancer cell line MCF-7 and downregulates cytochrome P4501B1 through the COX-2/PGE2 pathway. Oncology Reports, 28, 2131-2137. https://doi.org/10.3892/or.2012.2031
MLA
Yuan, L., Jiang, R., Yang, Y., Ding, S., Deng, H."1,25-Dihydroxyvitamin D3 inhibits growth of the breast cancer cell line MCF-7 and downregulates cytochrome P4501B1 through the COX-2/PGE2 pathway". Oncology Reports 28.6 (2012): 2131-2137.
Chicago
Yuan, L., Jiang, R., Yang, Y., Ding, S., Deng, H."1,25-Dihydroxyvitamin D3 inhibits growth of the breast cancer cell line MCF-7 and downregulates cytochrome P4501B1 through the COX-2/PGE2 pathway". Oncology Reports 28, no. 6 (2012): 2131-2137. https://doi.org/10.3892/or.2012.2031