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

Yalin Wang, Yi Dong, Yingmin Liu, Ziling Liu

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.