Bortezomib and Arsenious Acid Synergistically Inhibit HL-60 Cells Viability in vitro and in vivo

Title:Bortezomib and Arsenious Acid Synergistically Inhibit HL-60 Cells Viability in vitro and in vivo

Volume: 9 Issue: 1

Author(s): Yunbi Fu, Li li, Qixin Sun and Fanyi Meng

Affiliation:

Keywords: Apoptosis, arsenious acid, bortezomib, leukemia, mice xenograft model.

Abstract: Aims: We investigated whether bortezomib synergizes with arsenious acid in killing promyelocytic leukemia HL-60 cells in vitro and in vivo.

Main Methods: Cell culture, MTT assay, Hoechest 33324 staining, flow cytometry assay, determination of DNA fragmentation, immunoblotting analysis, HL60 xenograft mice models and animal experiments.

Key Findings: Bortezomib inhibited proliferation of HL-60 cells in a time- and dose-dependent manner. 20nM bortezomib enhanced the cytotoxic effect of arsenious acid. Consistent with the results in vitro, bortezomib or arsenious acid alone exhibited antitumor activity in HL-60 cell-xenografted mice, whereas combined bortezomib and arsenious acid treatment showed a greater antitumor activity than single treatment. The mice tolerated the drugs with no obvious side-effects. Further mechanistic study found that bortezomib induced cell apoptosis associated with activation of the caspase cascade, including down-regulation of Bcl-2 and cleavage of caspase family members and PARP.

Significance: These results demonstrate that the combination of bortezomib and arsenious acid could be more effective than single agent in inhibiting HL-60 cells viability.

Cite this article as:

Fu Yunbi, li Li, Sun Qixin and Meng Fanyi, Bortezomib and Arsenious Acid Synergistically Inhibit HL-60 Cells Viability in vitro and in vivo, Current Signal Transduction Therapy 2014; 9 (1) . https://dx.doi.org/10.2174/157436240901140924101815