Mechanism Of The Growth-promoting Effect Of Angiotensinâ…¡ And Angiotensinâ…¡ Receptor On The Leukemic Cells

Part1 Effect of AngiotensinⅡon Leukemic Cells Growth and AngiotensinⅡReceptor Expression on Human Leukemic CellObjective: To study the effect of angiotensinⅡon leukemic cells, growth and the expression of angiotensinⅡreceptor in human leukemic cells.To explore the relation of angiotensinⅡand it,s receptors to leukemia development.Make a new method to study the leukemia pathogenesis.Methods: Human K562 leukemia cells as research object were cultured in vitro in RPMI1640 medium. AngⅡact on K562 cell with various concentrations(0,10-9,10-8,10-7,10-6mol/L )and on different times(6h,12h,24h,48h)。The reaction of growth was detected by MTT method. Use immunohistochemical method to analyze the angiotensinⅡreceptor protein expression in bone marrow mononuclear cells of acute leukemia patient and thrombocytopenic purpura patients as control group.Results: Both leukemia group and control group bone marrow mononuclear cell all express the receptors in cell membrane and cytoplasm.In leukemic cell,the expression of angiotensinⅡtype 1 receptor is significantly higher than the expression of angiotensinⅡtype 2 receptor. In control group cell,the expression of angiotensinⅡtype 1 receptor is less than the expression of angiotensinⅡtype 2 receptor. AngⅡcan promote the growth of K562 cells in certain condition The cell growth was significantly increased by 6h to 12h incubation with 10-7mol/L AngⅡ. Conclusion: Both AT1 and AT2 receptors express in acute leukemic cells in membrane and cytoplasm,Which prompt the rennin-angiotensin system exist in bone marrow.The dominant expression of AngiotensinⅡReceptor type 1 in leukemic cell can possiblely contribute the development of leukemia. AngⅡcan promote the growth of K562 cells in the time and dose depended manner. Part2:Mechanism of the growth-promoting effect of AngⅡon K562 cells:a basic studyObjection:To study the effect of AngⅡreceptor antagonist on growth-promoting of K562 cells by AngⅡand AngⅡon K562 vascular endothelial growth factor (VEGF) secretion.To explore AngⅡ-mediated signaling pathways and influence of AngⅡon other growth factor. Method:Human K562 leukemia cells as research object were cultured in vitro in RPMI1640 medium. AngⅡreceptor antagonist(10-6mol/L) treated on K562 cells for 30min,then inhibitory reaction on AngⅡpromoting K562 cells growth was detected by MTT method. ELISA method was used to analyse the accommodation of AngⅡon VEGF secretion.Results: AngⅡcan promote the growth of K562 cells.The AngⅡinduced growth effects was completely blocked by pretreatment with the AT1R antagonist ,but not by AT2R antagonist.There was no apoptosis effect observed when the cells were treated with receptor antagonist alone (Valsartan,PD123319). AngⅡcan stimulate the autocrine of VEGF in K562 cells.Conclusion: AngⅡcan promote the growth of K562 cells.the growth-promoting effect can be inhibited by AT1R antagonist and not byAT2R antagonist. Valsartan treating K562 cell alone had not effect on the cell growth. AngⅡcan increase the K562 cells autocrine of VEGF by activing AT1R,promoting leukemia angiogenesis.