Objective: This paper was to study the reversal effect of magnetic Nano-Fe3O4 or Nano-Au with DNR, on multidrug resistance cell line K562/A02 and to investigate the reversal mechanism of this combination, and to provide theoretic evidence for the clinical application of them as resistance modifying agents.
Method: The IC50 (the concentration causing 50% inhibition of cell growth) of DNR, Nano-Fe3O4 and Nano-Au respectively were assayed by MTT method.The drug-loaded nanoparticles were prepared by solvent diffusion method.Some nanoparticales, volume ratio from 1.5% to 50%, were combined with some DNR to find the best combination to prepare best drug-loaded nanopartilces.At last, the K562/A02 cells was treated with the composite of 25% nanoparticales and 10mg/L DNR, which MDR1 mRNA was assayed by RT-PCR;intracellular drug concentration and the apoptosis was determined by fluorometry and confocal fluorescence microscope.
Results: The IC50 of DNR for K562/A02 and K562 cells were 23.23mg/L and0.307mg/L respectively.Two nanoparticles themselves have not evident cytotoxic effect to K562/A02 and K562 cells.Pretreating K562/A02 cells with the composite of 25% nanoparticales and 10mg/L DNR for 48 hours partially restored the sensitivity of K562/A02 cells to DNR;K562/A02 showed apoptotic characteristics after treated with this composite;drug-loaded nanopartilces elevated the intracellular DNR accumulation in K562/A02 and its MDR1 mRNA were down regulated.Data was analyzed by SPSS 11.5 software and expressed as mean ± SD.
Conclusions:
Nano- Fe3O4 or Nano-Au can increases the intracellular free DNR concentration of the K562/A02 cells, which lead to more K562/A02 cells apoptosis.
Two nanoparticles themselves could not lower the MDR1 gene expression of the K562/A02 cells, but they degraded the MDR1 gene level with combine DNR.
These results suggested that Nano- Fe3O4 or Nano-Au with DNR can reverse the resistance of K562/A02 cells significantly.
Disclosure: No relevant conflicts of interest to declare.
