Reversal effects of milbemycins on multidrug resistance in MCF-7/adr cells

Abstract

Aim To explore the reversal of MDR(multidrug resistance) by nemadectin and milbemycin β1 from the milbemycin family to adriamycin-resistant human breast carcinoma cells(MCF-7 / adr). Methods MTT assay was used to evaluate the cell suppression rates and reversal effects. Intracellular accumulation of adriamycin was determined by HPLC. The accumulation of rhodamine 123(Rh123) was measured with spectrofluorometer. The expressions of P-gp and the MDR1 gene encoding P-gp were tested by flow cytometry and reverse-transcriptase PCR. Results Nemadectin and milbemycin β1at the high dose of 5 μmol·L- 1significantly increased the sensitivity of MCF-7 / adr cells to adriamycin. They also increased the intracellular accumulation of adriamycin and Rh123 in MCF-7 /adr cells in a dose-dependent manner. Expression of both P-gp and MDR1 was down-regulated to different level. Conclusion Nemadectin and milbemycin β1can partly reverse multidrug resistance of MCF-7 / adr,and the effect of nemadectin is better than that of milbemycin β1.