Abstract 596: Low-dose 1,25-dihydroxyvitamin D3 combined with arsenic trioxide synergistically inhibits proliferation of acute myeloid leukemia cells by promoting apoptosis.

Abstract

Abstract Arsenic trioxide (As2O3) has shown substantial efficacy in the treatment of patients with acute promyelocytic leukemia (APL). However, since not all patients can achieve remission after treatment, it is necessary to investigate a novel method to overcome the problem. We investigated the anti-leukemic effect of low-dose 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in combination with As2O3 on HL-60 and K562 cells. The cell viability was in reverse proportion to As2O3 or 1,25(OH)2D3 concentration. In both HL-60 and K562 cells, after the combination treatment with As2O3 and 1,25(OH)2D3 at a 10:1 ratio, the combination index values were less than 1 in all treatment groups. In the RT-PCR and Western blot analysis, the combination treatment decreased Bcl-2 expression and increased Bax and Caspase-3 expressions more prominently than the single treatment. In the flow cytometric analysis performed in HL-60 cells, the proportion of late apoptosis was 4.9% in control, 30.0% in 1.0 μM As2O3, 8.1% in 100nM 1,25(OH)2D3, and 64.3% in 1.0 μM As2O3 plus 100 nM 1,25(OH)2D3. In conclusion, low-dose 1,25(OH)2D3 combined with As2O3 synergistically inhibited proliferation of HL-60 and K562 cells. In addition, this combination activated the apoptosis pathway more prominently than the single-drug treatment. Citation Format: Bae Ji-Yeon, Ji-Won Kim, Inho Kim. Low-dose 1,25-dihydroxyvitamin D3 combined with arsenic trioxide synergistically inhibits proliferation of acute myeloid leukemia cells by promoting apoptosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 596. doi:10.1158/1538-7445.AM2013-596