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Synergistic suppression effect on tumor growth of acute myeloid leukemia by combining cytarabine with an engineered oncolytic vaccinia virus

Authors Peng J, Wang S, Fan W, Li S, Wu Y, Mou X, Wang J, Tong X

Received 23 April 2018

Accepted for publication 19 July 2018

Published 15 October 2018 Volume 2018:11 Pages 6887—6900

DOI https://doi.org/10.2147/OTT.S172037

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Arseniy Yuzhalin


Jiamin Peng,1,* Shibing Wang,2,3,* Weimin Fan,1,* Shuangshuang Li,2,3 Yi Wu,4 Xiaozhou Mou,2,3 Jianchao Wang,1,5 Xiangmin Tong1–3

1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China; 2Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China; 3Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310014, China; 4Department of Hematology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China; 5Department of Clinical Laboratory, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310015, China

*These authors contributed equally to this work

Background: In consideration of the drug resistance and side effects associated with cytarabine, one of the most effective drugs for the treatment of acute myeloid leukemia (AML), there is a need for safer and effective strategies.
Methods: In the present investigation, we fabricated a new oncolytic vaccinia virus (oVV-ING4), which expresses the inhibitor of growth family member 4 (ING4) and explored its antitumor activity individually and in combination with cytarabine in AML cells.
Results: The experiments confirmed that oVV can efficiently and specifically infect leukemia cells, and augment the ING4 gene expression. Flow cytometry and western blot demonstrated that oVV-ING4 enhances apoptosis and G2/M phase arrest in AML cells, and causes remarkable cancer cell death. In addition, the synergistic efficiency of oVV-ING4 and cytarabine was investigated in vitro and in vivo; the combination significantly inhibited the survival of leukemia cells in vitro and xenografted KG-1 AML tumor growth in vivo.
Conclusion: In brief, oVV-ING4 can increase the sensitivity of leukemia cells to cytarabine and induce cell apoptosis in vitro and in vivo. Thus, oVV-ING4 may be a promising therapeutic candidate for leukemia and in combination with cytarabine represents a potential antitumor therapy.

Keywords: oncolytic vaccinia virus, acute myeloid leukemia, combination therapy, ING4, cytarabine

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