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

Abstract

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.