Radiation-sensitising effects of antennapedia proteins (ANTP)-SmacN7 on tumour cells

• Published in: International journal of molecular sciences 2013-12, Vol.14 (12), p.24087-24096
• Main Authors: Du, Li Qing, Wang, Yan, Xu, Chang, Cao, Jia, Wang, Qin, Zhao, Hui, Fan, Fei Yue, Wang, Bing, Katsube, Takanori, Fan, Sai Jun, Liu, Qiang
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antennapedia Homeodomain Protein - chemistry; Antennapedia Homeodomain Protein - genetics; Antennapedia Homeodomain Protein - metabolism; ANTP-smacN7 fusion protein; Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Caspase 3 - metabolism; Caspase 9 - metabolism; Cell Line, Tumor; Electronic mail systems; Fluorescent Dyes - chemistry; Gamma Rays; HeLa Cells; Humans; Mitochondria - drug effects; Mitochondria - metabolism; Molecular Sequence Data; Oligopeptides - chemistry; Oligopeptides - genetics; Oligopeptides - metabolism; Peptides; Permeability - drug effects; Permeability - radiation effects; Protein expression; Proteins; Radiation therapy; Radiation Tolerance - drug effects; Radiation-Sensitizing Agents - chemistry; Radiation-Sensitizing Agents - metabolism; Radiation-Sensitizing Agents - pharmacology; radiosensitivity; Receptors, Death Domain - metabolism; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - pharmacology; Tumors; X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors; X-Linked Inhibitor of Apoptosis Protein - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms141224087

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.