Esketamine Regulates Glutaminolysis in Endometrial Cancer via LDHA-HIF1A Pathway

doi:10.3870/j.issn.1672-8009.2026.02.001

Abstract

Abstract: Objective To investigate the mechanism of esketamine(ESK)in modulating the glutaminolysis in endometrial cancer(EC)via the lactate dehydrogenase A(LDHA)-hypoxia-inducible factor 1A(HIF1A)axis.Methods Human EC cell line KLE was treated with 0-10 μmol/L ESK.5 μmol/L was selected as the working concentration.The LDHA overexpression/knockdown and HIF1A overexpression models were constructed,and cell proliferation,invasion,apoptosis,glutamine uptake,adenosine triphosphate level and glutaminase(GLS)expression were measured.A C57BL/6 xenograft model was established to assess tumor growth inhibition by ESK,levels of LDHA,HIF1A and GLS in tumors were measured.Results ESK significantly inhibited KLE cell proliferation and invasion and promoted the apoptosis(P<0.05).Overexpression of LDHA reversed these effects and enhanced glutaminolysis,whereas ESK abrogated the effect of LDHA overexpression.LDHA knockdown reduced metabolic activity and malignant phenotypes,and HIF1A overexpression partially rescued these results.Xenograft experienment showed that ESK suppressed tumor growth and levels of LDHA,HIF1A and GLS in tumor tissues(P<0.05).Conclusion ESK blocks the LDHA-HIF1A pathway,inhibits glutaminolysis,proliferation and invasion,and promotes apoptosis in EC.

Key words: esketamine, glutaminolysis, endometrial cancer, lactate dehydrogenase A, hypoxia-inducible factor 1A

CLC Number:

R737.33

ZHOU Guanghua, ZHU Teng, WU Yumei. Esketamine Regulates Glutaminolysis in Endometrial Cancer via LDHA-HIF1A Pathway[J]. Journal of Medical Molecular Biology, 2026, 23(2): 107-115.

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