Abstract
The objective of this study was to investigate the underlying mechanisms behind the radiation-sensitising effects of the antennapedia proteins (ANTP)-smacN7 fusion protein on tumour cells. ANTP-SmacN7 fusion proteins were synthesised, and the ability of this fusion protein to penetrate cells was observed. Effects of radiation on the expression of X-linked inhibitor of apoptosis protein (XIAP) were detected by western blotting. The radiation-sensitising effects of ANTP-SmacN7 fusion proteins were observed by a clonogenic assay. The effects of drugs and radiation on tumour cell apoptosis were determined using Annexin V/FITC double staining. Changes in caspase-8, caspase-9 and caspase-3 were detected by western blot before and after ANTP-SmacN7 inhibition of XIAP. The ANTP-SmacN7 fusion protein could enter and accumulate in cells; in vitro XIAP expression of radiation-induced tumour cells was negatively correlated with tumour radiosensitivity. The ANTP-SmacN7 fusion protein promoted tumour cell apoptosis through the activation of caspase3. ANTP-SmacN7 fusion protein may reduce tumour cell radioresistance by inducing caspase3 activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antennapedia Homeodomain Protein / chemistry
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Antennapedia Homeodomain Protein / genetics
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Antennapedia Homeodomain Protein / metabolism*
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Apoptosis / drug effects*
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Apoptosis / radiation effects
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Caspase 3 / metabolism
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Caspase 9 / metabolism
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Cell Line, Tumor
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Fluorescent Dyes / chemistry
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Gamma Rays
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HeLa Cells
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Humans
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Mitochondria / drug effects
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Mitochondria / metabolism
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Molecular Sequence Data
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Oligopeptides / chemistry
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Oligopeptides / genetics
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Oligopeptides / metabolism*
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Permeability / drug effects
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Permeability / radiation effects
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Radiation Tolerance / drug effects*
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Radiation-Sensitizing Agents / chemistry
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Radiation-Sensitizing Agents / metabolism
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Radiation-Sensitizing Agents / pharmacology*
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Receptors, Death Domain / metabolism
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / pharmacology
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X-Linked Inhibitor of Apoptosis Protein / antagonists & inhibitors
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X-Linked Inhibitor of Apoptosis Protein / metabolism
Substances
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Antennapedia Homeodomain Protein
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Fluorescent Dyes
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Oligopeptides
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Radiation-Sensitizing Agents
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Receptors, Death Domain
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Recombinant Fusion Proteins
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SMAC peptide
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X-Linked Inhibitor of Apoptosis Protein
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Caspase 3
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Caspase 9