Document Type : Original Article(s)
Authors
- mehrshad shams 1
- tamana eskandari 2
- amirmohammad roshanfekr 1, 3
- amir kahrizi 1
- hossein asgarian-omran 1, 4
- reza valadan 1, 5
- mohsen tehrani 1, 5
- saeid taghiloo 1, 5
1 Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
2 Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
3 Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
4 Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran
5 Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran
Abstract
Background: Acute myeloid leukemia (AML) cells adapt to low oxygen by activating hypoxia‑inducible factor 1‑alpha (HIF-1α), which increases lactate dehydrogenase A (LDHA) and autophagy. This helps them rely more on glycolysis and may contribute to a metabolically hostile microenvironment, making treatment harder. Blocking HIF-1α and LDHA could disrupt these survival strategies and improve treatment success. Therefore, the present study aimed to investigate the effects of HIF-1α and LDHA inhibition on the expression of key glycolysis- and autophagy-related genes in HL‑60 (AML) and K562 (CML‑derived) cell lines.
Method: In this in-vitro experimental study, bioinformatics analysis of gene expression data from 183 AML patients and 10 controls revealed significant upregulation of HIF-1α and LDHA in the AML samples, which were visualized through heatmaps and volcano plots using R software. Then, HL‑60 (AML) and K562 chronic myeloid leukemia (CML‑derived control) cell lines were treated with Silibinin and Sodium Oxamat, HIF-1α and LDH-A inhibitor, respectively. The quantification of GLUT1, HK2, PKM2, ATG5, BECLIN-1, and ATG7 mRNA expression via the quantitative reverse-transcription polymerase chain reaction.
Results: HIF-1α and LDHA are upregulated in AML and critical for cell survival. Silibinin and Sodium Oxamate reduce AML cell viability but induce heterogeneous changes in glycolytic and autophagy genes expression, reflecting metabolic adaptations.
Conclusion: Our study shows that targeting HIF-1α and LDHA inhibits AML cell survival by disrupting glycolysis and autophagy pathways. This approach may overcome metabolic adaptations in AML and improve therapeutic outcomes.
Highlights
Saeid Taghiloo (google scholar)
Keywords
Main Subjects
Please cite this article as: Shams M, Eskandari T, Roshanfekr A, Kahrizi A, Asgarian-Omran H, Valadan R, et al. The Impact of HIF-1α and LDHA Inhibition on the Expression of Autophagy and Glucose Metabolism Pathway Genes in HL‑60 and K562 Cell Lines. Middle East J Cancer. 2026: in press. doi: 10.30476/mejc.2026.110670.2407.
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