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

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

Journal Name: Current Signal Transduction Therapy

Volume 9 , Issue 1 , 2014

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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.

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

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Article Details

VOLUME: 9
ISSUE: 1
Year: 2014
Page: [1 - 8]
Pages: 8
DOI: 10.2174/157436240901140924101815

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