Resistance to chemotherapy is associated with altered glucose metabolism in acute myeloid leukemia

Song,Kui; Li,Min; Xu,Xiaojun; Xuan,Li; Huang,Guinian; Liu,Qifa

doi:10.3892/ol.2016.4600

Resistance to chemotherapy is associated with altered glucose metabolism in acute myeloid leukemia

Authors:
- Kui Song
- Min Li
- Xiaojun Xu
- Li Xuan
- Guinian Huang
- Qifa Liu
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Affiliations: Department of Hematology, The First Affiliated Hospital of Jishou University, Jishou, Hunan 416000, P.R. China, Department of Pharmacy, The First Affiliated Hospital of Jishou University, Jishou, Hunan 416000, P.R. China, Department of Hematology, Zhongshan City People's Hospital, Zhongshan, Guangdong 528400, P.R. China, Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: May 17, 2016 https://doi.org/10.3892/ol.2016.4600
Pages: 334-342

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Abstract

Altered glucose metabolism has been described as a cause of chemoresistance in multiple tumor types. The present study aimed to identify the expression profile of glucose metabolism in drug-resistant acute myeloid leukemia (AML) cells and provide potential strategies for the treatment of drug‑resistant AML. Bone marrow and serum samples were obtained from patients with AML that were newly diagnosed or had relapsed. The messenger RNA expression of hypoxia inducible factor (HIF)-1α, glucose transporter (GLUT)1, and hexokinase‑II was measured by quantitative polymerase chain reaction. The levels of LDH and β subunit of human F1‑F0 adenosine triphosphate synthase (β‑F1‑ATPase) were detected by enzyme‑linked immunosorbent and western blot assays. The HL‑60 and HL‑60/ADR cell lines were used to evaluate glycolytic activity and effect of glycolysis inhibition on cellular proliferation and apoptosis. Drug‑resistant HL‑60/ADR cells exhibited a significantly increased level of glycolysis compared with the drug‑sensitive HL‑60 cell line. The expression of HIF‑1α, hexokinase‑II, GLUT1 and LDH were increased in AML patients with no remission (NR), compared to healthy control individuals and patients with complete remission (CR) and partial remission. The expression of β‑F1‑ATPase in patients with NR was decreased compared with the expression in the CR group. Treatment of HL‑60/ADR cells with 2‑deoxy‑D‑glucose or 3‑bromopyruvate increased in vitro sensitivity to Adriamycin (ADR), while treatment of HL‑60 cells did not affect drug cytotoxicity. Subsequent to treatment for 24 h, apoptosis in these two cell lines showed no significant difference. However, glycolytic inhibitors in combination with ADR increased cellular necrosis. These findings indicate that increased glycolysis and low efficiency of oxidative phosphorylation may contribute to drug resistance. Targeting glycolysis is a viable strategy for modulating chemoresistance in AML.

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