Combing oncolytic adenovirus expressing Beclin-1 with chemotherapy agent doxorubicin synergistically enhances cytotoxicity in human CML cells in vitro

Li LI1, Liang-shun YOU1, Li-ping MAO1, Shen-he JIN1, Xiao-hui CHEN2, Wen-bin QIAN1
1 Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
2 Department of Hematology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China
Correspondence to: Wen-bin QIAN:,
DOI: 10.1038/aps.2017.100
Received: 7 March 2017
Accepted: 9 July 2017
Advance online: 14 September 2017


Cancer virotherapy provides a new strategy to treat cancer that can directly kill cancer cells by oncolysis. Insertion of therapeutic genes into the genome of a modified adenovirus, thereby creating a so-called gene-virotherapy that shares the advantages of gene therapy and virotherapy. In this study we investigated whether a strategy that combines the oncolytic effects of an adenoviral vector with the simultaneous expression of the autophagy gene Beclin-1 offered a therapeutic advantage for chronic myeloid leukemia (CML) cells with resistance to chemotherapy and evaluated the synergistic effects of SG511-BECN and doxorubicin (Dox) in human CML cells in vitro. Oncolytic virus SG511-BECN was constructed through introducing the Beclin-1 gene into the oncolytic adenoviral backbone. SG511- BECN displayed significantly improved antileukemia activity on multidrug-resistant CML cell line K562/A02, which was mediated via induction of autophagic cell death. Furthermore, Dox could synergize with SG511-BECN to kill the CML cells by improving the infectious efficiency of the oncolytic adenovirus without causing significant damage to normal human mononuclear cells. The results demonstrate that targeting the autophagic cell death pathway and combination of a chemotherapy agent with oncolytic adenovirus may be a novel strategy for the treatment of leukemia with chemotherapy resistance.
Keywords: chronic myeloid leukemia; multidrug-resistant; K562/A02 cell line; doxorubicin; oncolytic adenovirus; Beclin-1; autophagy; apoptosis; synergy

Article Options

Download Citation

Cited times in Scopus