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.
Current Signal Transduction Therapy
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.
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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
DOI https://dx.doi.org/10.2174/157436240901140924101815 |
Print ISSN 1574-3624 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-389X |
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