Abstract

 Background and Objectives

 The efficacy of arsenic trioxide (ATO), as a poisonous drug, in the treatment of acute promyelocytic leukemia (APL) is widely accepted. Due to adverse effects associated with high-dose ATO, the combination therapy is a rational therapeutic strategy to enhance the effectiveness of ATO. In this regard, we used simvastatin (SV), a cholesterol lowering medication, and hypothesized that SV plus ATO would potentiate the efficacy of ATO at lower doses. 

 Materials and Methods

 To evaluate the effects of SV and ATO treatment (in isolation or in combination) on transcriptional levels of Bax and Bcl-2, apoptosis, growth kinetic, and metabolic activity of NB-4 cells, we employed RQ-PCR, flowcytometry, trypan blue dye exclusion, and MTT assays, respectively. The data were analyzed using SPSS 21, student’s t-test and one-way ANOVA tests.

 Results

 Both SV and ATO considerably hindered the metabolic activity of NB-4 cells in a concentration-dependent manner. In addition, the co-treatment with them exerted an indicative decline in viability, and a significant augmentation in apoptotic population and in the ratio of Bax to Bcl-2 mRNA level. 

 Conclusions

 Our results have demonstrated that ATO and SV cooperate synergistically to induce cell death and to inhibit the proliferation rate of NB-4 cells. Furthermore, our results suggest that the combination treatment increased the programmed cell death rate probably through enhancing the intrinsic mitochondrial apoptotic pathway. On aggregate and in view of these data, SV showed the potency for attenuating the effective dose of ATO.