| BackgroundMetformin is a well-established,effective agent for the management of type?,diabetes mellitus.Patients with diabetes mellitus are at increased risk of cancer development.Metformin is expected to be a new type of tumor therapy drugs or antitumor adjuvant.Leukemia is a malignant clonogenic disease of a class of hematopoietic stem cells,metformin is also expected to be a drug for the treatment of leukemia or adjuvant treatment of leukemia.However,the antitumor mechanism of metformin is not clear.AMPK pathway is an important pathway of metformin induced hypoglycemia,AMPK plays a role in regulating growth and survival of multiple cancer cells including leukemia cells and it may also be a molecular pathway for metformin.KG1 a cells are rich in cell subsets with LSC in line with phenotypes.ObjectiveTo study the effect of metformin on apoptosis of KG1 a cells and its molecular mechanism to provide evidence for the further study of metformin in the treatment of leukemia.Methods1.CCK8 assay was used to detect the inhibition of KG1 a cell proliferation Induced by metformin.2.Flow cytometry was used to detect the effect of metformin on apoptosis of KG1 a cells.3.Western blot was used to observe the changes of intracellular protein expression.Results1.Metformin inhibited the proliferation of KG1 a cells in a concentration-dependent manner.2.Metformin can induce apoptosis of KG1 a cells in a concentration-dependent manner.3.With the increase of drug concentration,the decreased expression of AKT,AMPK?,P70S6 K and 4EBP1 showed that Metformin could induce apoptosis of KG1 a cells.With the increase of drug concentration,phosphorylation of AKT increased,with the increase of drug concentration,the decreased phosphorylation level of AMPK?,P70S6 K and 4EBP1 indicated that metformin could inhibit AMPK pathway.ConclusionMetformin can induce apoptosis of KG1 a cells,and its mechanism of this action is related to the inhibition of AMPK pathway. |
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