Arsenic trioxide nanoparticles inhibit acute promyelocytic leukemia cell proliferation and induce apoptosis via PTEN/AKT signalling pathway

Abstract

Background: Arsenic Trioxide (As2O3) is a FDA-approved agent for the treatment of Acute Promyelocytic Leukemia (APL). But the high-toxicity is a bottleneck of the effect of As2O3. Methods: In our previous work, we made a novel nanoparticle formulation of As2O3. The aim of the present study was to preliminary study the possible mechanisms of the antitumor effect of As2O3 nanoparticles on NB4 cells. We examined the proliferation and apoptosis of NB4 cells incubated with the As2O3 or As2O3 nanoparticles. Protein levels of p-PTEN, p-AKT, Bax, caspase-3, caspase-9 and AIF of NB4 cells after using As2O3 nanoparticles and traditional As2O3 were determined by Western blotting analysis. Results: In vitro cytotoxicity test showed that the inhibition rate and apoptosis level of NB4 cells treated with As2O3 nanoparticles was much higher than that of traditional As2O3. Moreover, As2O3 nanoparticles resulted in a more significant increase in p-PTEN expression and a greater reduction in p- Akt expression compared with traditional As2O3. Conclusions: Our findings indicated the obvious anticancer effect of As2O3 nanoparticles and demonstrate the possible mechanism of its therapeutic potential. The results provide a foundation for the future clinical studies of As2O3 nanoparticles in APL patients.