Glucose induced-AKT/mTOR activation accelerates glycolysis and promotes cell survival in acute myeloid leukemia

作者全名："Chen, Shana; Tao, Yonghong; Wang, Qian; Ren, Jun; Jing, Yipei; Huang, Junpeng; Zhang, Ling; Li, Rufei"

作者地址："[Chen, Shana; Wang, Qian; Li, Rufei] Chonggang Gen Hosp, Dept Lab Med, Chongqing 400080, Peoples R China; [Tao, Yonghong; Ren, Jun; Jing, Yipei; Huang, Junpeng; Zhang, Ling] Chongqing Med Univ, Sch Lab Med, Minist Educ, Key Lab Lab Med Diagnost Designated, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Li, RF (通讯作者)，Chonggang Gen Hosp, Dept Lab Med, Chongqing 400080, Peoples R China."

来源：LEUKEMIA RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001029155200001

JCR分区：Q3

影响因子：2.7

年份：2023

卷号：128

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Acute myeloid leukemia; Glucose; Glycolysis; Cell survival; AKT; mTOR signaling pathway

摘要："Multiple studies have demonstrated that excessive glucose utilization is a common feature of cancer cells to support malignant phenotype. Acute myeloid leukemia (AML) is recognized as a heterogeneous disorder of hematopoietic stem cells characterized by altered glucose metabolism. However, the role of glucose metabolic dysfunction in AML development remains obscure. In this study, glucose and 2-Deoxy-D-glucose (2-DG) treat-ment were applied to analyze the relationship between glucose metabolism and cell survival. Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM) assays were used to examine the cell viability and apoptosis rate. Glucose consumption and lactate production were measured to assess the glucose metabolism pathway. The results demonstrated that abnormally increased glucose effectively promoted proliferation of leukemic cells and inhibited cell apoptosis, while 2-DG ameliorated leukemic phenotypes. Importantly, glucose exposure induced active glycolysis by increasing glucose consumption and lactate production. Furthermore, the levels of key glycolysis-related genes glucose transporter 1 (GLUT1) and monocarboxylate transporter 1 (MCT1) were upre-gulated. Mechanistic investigations revealed that AKT/mTOR signaling pathway was activated in glucose con-dition. In conclusion, our findings indicate that glucose induced-AKT/mTOR activation plays a growth-promoting role in AML, highlighting that inhibition of glycolysis would be a vital adjuvant therapy strategy for AML."

基金机构："Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau, China) [2021MSXM105]"

基金资助正文："This work was supported by Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau, China) (2021MSXM105) ."