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Title: Reversal effects of droloxifene on multidrug resistance in adriamycin-resistant K562 cell line.
Author: Li J, Xu LZ, Yao JJ, Guo WJ, Xia P, Chen Y.
Journal: Acta Pharmacol Sin; 2001 Nov; 22(11):1023-7. PubMed ID: 11749795.
Abstract:
AIM: To study the reversal effects of droloxifene (DRO) on multidrug resistance (MDR) in K562 cell line resistant to adriamycin (ADR). METHODS: K562 cell line resistant to ADR (K562/A02) and K562 cell line sensitive to ADR (K562) were treated with DRO. Using MTT assay, chemosensitivity to ADR in DRO-treated K562 cell lines was studied. Before and after the treatment with DRO 10 micromol/L, MDR1 and GSTpi gene expression were assayed by reverse transcription-polymerase chain reaction and immunocytochemistry assay. Flow cytometry was used to determine intracellular ADR concentration. RESULTS: DRO significantly reversed MDR in K562/A02 (P < 0.01). After treatment of DRO 20, 10, and 5 micromol/L, the chemosensitivity to ADR was increased to 14, 13, and 4 folds, respectively. The reversal activity of DRO was similar to that of verapamil (VRP). After treated with DRO 10 micromol/L, both MDR1 and GSTpi mRNA expression began to decline on the 2nd day, and significantly decreased on the 5th day (P<0.01). The changes in P-gp and GSTpi protein expression were similar to that of their mRNA expression. Two hours after treatment of DRO 20, 10, and 5 micromol/L, intracellular ADR concentration in K562/A02 was increased to 2.9, 2.3, and 1.5 folds, respectively. However, DRO did not markedly increase ADR accumulation in K562. CONCLUSION: DRO had strong reversal effect on MDR in K562/A02, which was comparable to that of VRP, but the reversal effect was via different pathways.

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