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

作　　者：Hongling Huang Tian Xiao Lingfeng He Hongbin Ji Xin-Yuan Liu 

机构地区：[1]State Key Laboratory of Cell Biology,Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China [2]Xinyuan Institute of Medicine and Biotechnology,Zhejiang Sci-Tech University,Hangzhou 310018,China [3]Department of Medicine,Beth Israel and Deaconess Medical Center,Harvard Medical School,Boston,MA 02215,USA

出　　处：《Acta Biochimica et Biophysica Sinica》2012年第9期737-745,共9页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China （30623003 and 81172449）; National Basic Research Program of China （973 Program） （2010CB529901 and 2011CB510104）;Important National Science ＆ Technology Specific Project of Hepatitis and Hepatoma Related Program （2008ZX10002- 023）; New Innovation Program （2009-ZX-09102-246）;and Zhejiang Sci-Tech University grant （1016834-Y）.

摘　　要：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.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.

关 键 词：IFN-Β cell cycle arrest APOPTOSIS NECROPTOSIS synergism 

分 类 号：Q255[生物学—细胞生物学] Q279