Mechanism Research of Reversal in Multidrug Resistance by Magnetic Nanoparticle Fe₃O₄ Syndesis with 5-Bromotetrandrine and Daunomycin

Objective To evaluate the MDR reversal activity of magnetic nanoparticle Fe₃O₄ (Nano-Fe₃O₄) and 5-bromotetrandrine (BrTet) on multidrug resistance cell line K562/A02 solitarily or symphysially, and to investigate the reversal mechanism of this coopration.

Methods The proliferation of K562 and K562/A02 cells which were cultured with daunomycin (DNR) alone or in combination with Nano-Fe₃O₄, BrTet or both for 48h were evaluated by MTT assay. DNR accumulation and P-gp of K562 and K562/A02 were analyzed by fluorospectrophotometry.

Results The IC50 of DNR for K562 and K562/A02 cells were 2.74±0.19μM and 32.33±8.40μM, respectively; but the sensitivity of K562/A02 cells to DNR was partially restored after culturing with Nano-Fe₃O₄, BrTet solitarily and symphysially (the IC50 were 7.04±0.85μM, 4.25±2.16μM, 1.80±0.30μM; the FR were 4.32, 7.61, 17.96, respectively), but had no effects on K562 cell lines. The differences had statistical significance. Flow cytometry assay showed that Nano-Fe₃O₄ and BrTet increased the DNR accumulation in K562/A02 cells, especially in the group of synergia of these two agents. The mean fluorescence intensity of endocellular DNR increased from 2614 pretreated with DNR only to 4783 incubated with these two reversal reagents, while the values were 3364, 4077 for incubating with Nano-Fe₃O₄ and BrTet respectively. P-gp were down regulated through pretreating with Nano-Fe₃O₄, BrTet alone and symphysially in K562/A02 cells by fluorospectrophotometry assay.

Conclusion Nano-Fe₃O₄ and BrTet synergisticly showed significant MDR reversal activity in vitro. The reversal activity may be related to the inhibition of P-gp overexpression and the increasing of the anticancer drug accumulation intracelluarly.