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The Nrf2/HO-1/HMGB 1 Signaling Pathway is Associated with Chemotherapy Resistance in K562/A02 Leukemia Cells
Pages: 129-135
Year: Issue:  2
Journal: Acta Laser Biology Sinica

Keyword:  leukemiachemotherapy resistancemultidrug resistancehigh mobility group protein 1 (HMGB1 )nu-clear factor erythroid 2-related factor 2 (Nrf2)heme oxygenase 1 (HO-1);
Abstract: Objective:By silencing the high mobility group protein 1 (HMGB1 )gene,the nuclear factor erythroid 2-re-lated factor 2 (Nrf2)gene,and the heme oxygenase 1 (HO-1)gene in chemotherapy-resistant leukemia cells (K562/A02 cell line),to explore the role of the Nrf2/HO-1/HMGB1 signaling pathway in leukemia chemotherapy resistance and its possible mechanism.Methods:The Adriamycin-resistant cell line K562/A02 were transfected with specific small interfering RNAs (siRNA)of HMGB1 gene,Nrf2 gene,and and HO-1 gene respectively.Fluorescence quantitative re-al-time polymerase chain reaction was used to examine the mRNA expression levels of HMGB1,Nrf2,and HO-1.West-ern blot was used to determine the protein expression levels of HMGB1,Nrf2,and HO-1.The Nrf2 protein expression level was detected by immunofluorescence assay.Cell viability of K562/A02 cell line was analyzed by Cell Counting Kit-8 before and after transfection.Results:Silencing of HMGB1,Nrf2,or HO-1 in K562/A02 cell line enhanced cell via-bility and recovered chemosensitivity compared with the control group and the blank group (P<0.05 ).Conclusions:HMGB1 overexpression in K562/A02 cell line might lead to chemotherapy resistance to Adriamycin.The Nrf2/HO-1 signaling pathway might be involved in the HMGB1-induced chemotherapy resistance in K562/A02 cell line,and its up-regulation might recover chemosensitivity.
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