title: In vivoandin vitroeffects of heme oxygenase-1 silencing on the survival of acute myelocytic leukemia-M2 cells.
abstract: The aim of this study was to investigate thein vivoandin vitroeffects 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.
authors: 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.
authors: Sixi
authors: S
authors: Wei
authors: 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.
authors: Yating
authors: Y
authors: Wang
authors: 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.
authors: Qixiang
authors: Q
authors: Chai
authors: Department of Pharmacy, The Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.
authors: Qin
authors: Q
authors: Fang
authors: 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.
authors: Yaming
authors: Y
authors: Zhang
authors: 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.
authors: Jishi
authors: J
authors: Wang
keywords: apoptosis; heme oxygenase-1; infiltration; proliferation