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Study On The Mitochondrial Autophagy Pathway Of Apoptosis Induced By Deferoxamine In The Leukaemia Cell Line HL-60

Posted on:2022-06-05Degree:MasterType:Thesis
Country:ChinaCandidate:Z J ZhuFull Text:PDF
GTID:2504306323497774Subject:Academy of Pediatrics
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ObjectiveAcute leukaemia is one of the most common malignant tumors in children,and it is mainly treated with combination chemotherapy and hematopoietic stem cell transplantation.At present,there are many problems in these treatments,such as large adverse reactions,easy to drug resistance and early recurrence.Our previous studies have found that deferoxamine can decrease the mitochondrial membrane potential of HL-60 cells,and release the cytochrome C from the mitochondrial adventitia,which regulates the mitochondrial mediated apoptosis pathway in the upstream.Western blot showed that DFO could induce mitochondrial autophagy phase protein NIX expression increased.There are no reports about the treatment of leukemia by mitophapy pathway.The purpose of this study is to explore the role of mitochondrial autophagy-mediated apoptosis pathway in DFO-induced apoptosis of HL-60 cells,and to provide an another experimental basis for the clinical treatment of leukemia with DFO.MethodsThe purpose of this study is to clarify the role of mitochondrial autophagy in DFO-induced apoptosis of HL-60 cells at cellular and molecular levels and to explore the mechanism of mitochondrial autophagy regulation.We intend to prove that DFO could induce apoptosis in HL-60 by Hoechst 33342 staining and Annevix V-APC/7-AAD double staining.Through the determination of intracellular ROS level,western blot detection of mitochondrial related protein expression of HSP60,NIX,TIMM23 and TOMM20,real-time fluorescence quantitative PCR detection of the RNA expression of NIX,LC3 and TIMM23 and fluorescence co-localization,we design to demonstrate that DFO can induce mitochondrial autophagy in HL-60 cells.ResultsDFO could induce apoptosis and mitochondrial autophagy in HL-60 cells.ConclusionsThis study explored the role of mitochondrial autophagy in DFO-induced apoptosis of HL-60 cells from a new perspective of mitochondrial autophagy.It has demonstrated that DFO can induce apoptosis and mitochondrial autophagy in HL-60 cells.Deferoxamine induced apoptosis of HL-60 through mitochondrial autophagy,which provide an another experimental basis for the clinical treatment of leukemia with DFO.
Keywords/Search Tags:mitochondrial autophagy, deferoxamine, leukaemia, apoptosis
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