and effects of heme oxygenase-1 silencing on the survival of acute myelocytic leukemia-M2 cells
Authors: Jishi Wang
Qixiang Chai
Qin Fang
Yaming Zhang
Yating Wang
Sixi Wei
Journal: Experimental and therapeutic medicine (2015)
Discipline: CLINICAL MEDICINE
Keywords: apoptosis; heme oxygenase-1; infiltration; proliferation.
Affiliations: Department of Hematology, The Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China ; Hematopoietic Stem Cell Transplantation Center of Guizhou Province, The Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China ; Department of Clinical Biochemistry, The Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China., Department of Hematology, The Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China ; Hematopoietic Stem Cell Transplantation Center of Guizhou Province, The Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China., Department of Pharmacy, The Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.

Abstract:  The aim of this study was to investigate the in vivo and in vitro effects of targeted heme oxygenase-1 (HO-1) silencing on the proliferation and apoptosis of human acute myelocytic leukemia (AML)-M2 cells. Bone marrow mononuclear cells (BMMNCs) were infected by pRNAi-siHO-1-GFP. The viability of the BMMNCs was determined by cell counting kit-8 (CCK-8) assay following daunorubicin (DNR) treatment. The apoptotic rate was detected by flow cytometry. The expression levels of HO-1 and apoptosis-related genes were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis. An AML-M2 xenograft mouse model was established. The tumor formation outcomes and survival were observed. The leukocyte and platelet counts and hemoglobin levels were monitored, and the copy numbers of AML1/ETO fusion gene were detected by qPCR. pRNAi-siHO-1-GFP silenced the expression of HO-1. DNR inhibited cell viability in a time- and dose-dependent manner. The survival rate of the cells was significantly reduced by infection with pRNAi-siHO-1-GFP. HO-1 expression in the BMMNCs infected with pRNAi-siHO-1-GFP was downregulated, whereas caspase-3, -8 and -9 expression was upregulated compared with that in control BMMNCs. Kasumi-1 cells were successfully inoculated into nude mice. The rats inoculated with pRNAi-siHO-1-GFP-transfected Kasumi-1 cells succumbed to tumors more slowly and survived longer than those inoculated with untransfected Kasumi-1 cells. Furthermore, the leukocyte and platelet counts and hemoglobin levels were higher and the copy numbers of AML1/ETO fusion gene were lower in the former group. HO-1 gene silencing may promote the apoptosis of human M2 leukemic cells by inhibiting a caspase-dependent apoptotic pathway. Targeted silencing of HO-1 is able to inhibit the proliferation and infiltration of leukemic cells in nude mice and thus prolong their survival. The findings provide valuable experimental evidence for the molecular targeted therapy of M2 leukemia. 

Retracted: No

PubPeer comments:
 This paper was found during a systematic search of papers in this journal with possible duplicated images. About 10% of the papers in this journal (n=169 examined) were found to contain inappropriately duplicated images. These papers have all been reported to the journal publisher in 2017. The editors promised to  investigate promptly but no action has been taken as of today. Figure 4A: Unexpected similarities between 2 different flow cytometry panels. Boxes of the same color draw attention to constellations that look more different than expected.  ,