Reversal Effect and Mechanism of 15-PGHD Induction Drugs on the Multidrug Resistance of Human Breast Cancer Cell Line MCF-7/ADR / 中国药学杂志

ABSTRACT

OBJECTIVE: To examine the expression of 15-hydroxyprostaglandin dehydrogenase(15-PGDH) in human multidrug-resistant breast cancer line MCF-7/ADR and to explore the reversal effect and mechanism of 15-PGHD induction drugs on MCF-7/ADR cells. METHODS: The RT-PCR and Western blot were used to detect 15-PGDH, COX-2 mRNA and protein expression in MCF-7 and MCF-7/ADR cells. PGE2 levels in supernatant of cells were determined by ELISA assay. Anti-proliferation effect and chemotherapy sensitivity to ADM of 15-PGDH induction drugs (indomethacin, ibuprofen and pioglitazone, dexamethasone) on breast cancer cells were assayed by MTT method. Cell apoptosis was detected by Hochest 33258 stain assay. RESULTS: Compared with MCF-7 cells, the 15-PGDH expression was significantly decreased, COX-2 expression was significantly increased and PGE2 levels in cell supernatant were increased in MCF-7/ADR cells. 15-PGDH induction drugs (indomethacin, ibuprofen and pioglitazone, dexamethasone) increased 15-PGDH expression or both reduced COX-2 expression, and finally reduced PGE2 levels in MCF-7/ADR cells. Effect of chemosensitivity and apoptosis induction of ADM was enhanced and multidrug resistance was partially reversed when co-treated with 15-PGDH induction drugs. CONCLUSION: The expression of 15-PGDH is decreased in human multidrug-resistant breast cancer line MCF-7/ADR. 15-PGDH induction drugs could increase chemosensitivity, promote apoptosis and reverse resistance of MCF-7/ADR cell, the mechanism might related to the influence of PGE2 level by regulated the expression of 15-PGDH and COX-2.