Effect of HIF-1α and LDHA Blockade on Gene Expression of Tumor Immune Evasion in Myeloid Leukemia Cell Lines

Authors
Tamana Eskandari 1
Mehrshad Shams 2
Ali Khanari 2
Amir Kahrizi 2
Hossein Asgarian-Omran 3
Reza Valadan 4
Mohsen Tehrani 4
Saeid Taghiloo 5
1 Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
2 Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
3 Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran
4 Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran
5 Thalassemia Research Center, Hemoglobinophaty Institute, Mazandaran University of Medical Sciences, Sari, Iran
10.66224/ibj.5324
Abstract
Background: Tumor cells utilize metabolic reprogramming to obtain the energy required for rapid proliferation. In this study, we blocked two key factors, hypoxia-inducible factor 1-alpha (HIF-1α) and lactate dehydrogenase (LDHA), in the metabolic pathway in acute myeloid leukemia (AML) cell lines to evaluate their effect on the expression of genes involved in tumor evasion.

Methods: Silibinin and sodium oxamate, as HIF-1α and LDHA blockers, respectively, were used to treat K-562 and HL-60 cells. The MTT assay was used to assess cell viability, and quantitative reverse transcription PCR was used to measure the mRNA expression levels of PD-L1, CD47, and CD155.

Results: Both K-562 and HL-60 cells showed a significant decrease in CD47 expression. Additionally, HL-60 cells indicated a significant suppression of CD155 expression. In contrast, PD-L1 expression remained unchanged after treatment.

Conclusion: Our findings suggest that blocking signaling pathways involved in metabolic reprogramming of cancer cells could be a promising approach for modulating the expression of certain immune checkpoint ligands, warranting further investigation.


Keywords
Acute myeloid leukemia
Hypoxia
Lactates
Warburg effect