Reversal Effect and Mechanism of 15-PGHD Induction Drugs on the Multidrug Resistance of Human Breast Cancer Cell Line MCF-7/ADR
OUYANG Lin-qi1, WANG Sheng-feng2a, WEI Feng1, HUANG Li-hua2b, HUANG Juan-juan3, LIU Shi-kun2a*
1. Department of Pharmacy, First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha 410007, China; 2a.Department of Pharmacy, 2b.Medical Center Laboratory, The Third Xiangya Hospital of Central South University, Changsha 410013, China; 3. Department of Pharmacy, The First Hospital of Changsha, Changsha 410005, China;
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.
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OUYANG Lin-qi, WANG Sheng-feng, WEI Feng, HUANG Li-hua, HUANG Juan-juan, LIU Shi-kun. Reversal Effect and Mechanism of 15-PGHD Induction Drugs on the Multidrug Resistance of Human Breast Cancer Cell Line MCF-7/ADR. Chinese Pharmaceutical Journal, 2018, 53(16): 1352-1358.
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2018, Vol. 53 
