Interferon-β-armed oncolytic adenovirus induces both apoptosis and necroptosis in cancer cells

• Published in: Acta biochimica et biophysica Sinica 2012-09, Vol.44 (9), p.737-745
• Main Authors: Huang, Hongling, Xiao, Tian, He, Lingfeng, Ji, Hongbin, Liu, Xin-Yuan
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenovirus; Antibiotics, Antineoplastic - pharmacology; Apoptosis - drug effects; Apoptosis - physiology; Ataxia Telangiectasia Mutated Proteins; Blotting, Western; caspase; Cell Cycle Checkpoints - drug effects; Cell Cycle Checkpoints - physiology; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - physiology; DNA-Binding Proteins - metabolism; Doxorubicin - pharmacology; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; HEK293 Cells; Humans; IFN-α; Interferon-beta - genetics; Interferon-beta - metabolism; Interferon-beta - physiology; MCF-7 Cells; Microscopy, Confocal; Mutation; Necrosis; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Oncolytic Viruses - genetics; Protein-Serine-Threonine Kinases - metabolism; S Phase - drug effects; S Phase - physiology; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins - metabolism; 坏死; 干扰素; 细胞凋亡; 肿瘤细胞; 腺病毒; 诱导
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gms060

Interferon-β （IFN-β） has been widely used in cancer therapy, but the clinical trial results are generally disappointing. Our previous studies have shown that an oncolytic adenovirus carrying IFN-β （ZD55-IFN-β） exhibits significant anti-tumor activities. However, the underlying mechanisms are not clear. Here we showed that ZD55- IFN-β infection-induced S-phase cell cycle arrest in a p53-dependent manner by activating the ataxia telangiectasia mutated-dependent DNA damage pathway. In addition, ZD55-IFN-β infection could initiate both caspase-dependent apoptosis and necroptosis in cancer cells. More importantly, ZD55-IFN-β showed a synergistic effect on cancer cells when combined with doxorubicin. These results suggest that the combination of ZD55-IFN- β with doxorubicin may represent a promising clinical strategy in cancer therapy.