艾司氯胺酮通过LDHA-HIF1A通路调节子宫内膜癌中的谷氨酰胺代谢

doi:10.3870/j.issn.1672-8009.2026.02.001

医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (2): 107-115.doi: 10.3870/j.issn.1672-8009.2026.02.001

• 论著 • 下一篇

艾司氯胺酮通过LDHA-HIF1A通路调节子宫内膜癌中的谷氨酰胺代谢

周广华¹, 朱腾¹, 吴玉梅²

首都医科大学附属北京妇产医院/北京妇幼保健院¹麻醉科,²妇科北京市,100026

收稿日期:2025-06-12 出版日期:2026-03-31 发布日期:2026-04-03
通讯作者: 周广华(E-mail:zhouguanghua@ccmu.edu.cn)
基金资助:
首都卫生发展科研专项(No.2024-1-2112)

Esketamine Regulates Glutaminolysis in Endometrial Cancer via LDHA-HIF1A Pathway

ZHOU Guanghua¹, ZHU Teng¹, WU Yumei²

¹Department of Anesthesiology,²Department of Gynecology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University/ Beijing Maternal and Child Health Care Hospital,Beijing,100026,China

Received:2025-06-12 Online:2026-03-31 Published:2026-04-03
Contact: ZHOU Guanghua(E-mail:zhouguanghua@ccmu.edu.cn)
Supported by:
Capital Health Development Research Special Project(No.2024-1-2112)

摘要/Abstract

摘要： 目的探讨艾司氯胺酮(esketamine,ESK)通过乳酸脱氢酶A(lactate dehydrogenase A,LDHA)-缺氧诱导因子1A(hypoxia-inducible factor 1A,HIF1A)轴调控子宫内膜癌(endometrial cancer,EC)谷氨酰胺代谢的机制。方法以0~10 μmol/L ESK干预人EC细胞KLE,选5 μmol/L为工作浓度。构建过表达/敲减LDHA及过表达HIF1A模型,测定细胞增殖、侵袭、凋亡、谷氨酰胺摄取、三磷酸腺苷及谷氨酰胺酶(glutaminase,GLS)表达。建立C57BL/6荷瘤小鼠,观察ESK对荷瘤小鼠的抑瘤率及肿瘤组织中LDHA、HIF1A、GLS表达的影响。结果 ESK显著抑制KLE增殖、侵袭并促凋亡(P<0.05);过表达LDHA可逆转上述效应并增强谷氨酰胺代谢,ESK可抑制该过程。敲减LDHA降低代谢与恶性表型,过表达HIF1A可部分挽回以上结果。动物实验显示ESK能够抑制荷瘤小鼠肿瘤生长,并下调肿瘤组织中LDHA、HIF1A、GLS水平(P<0.05)。结论 ESK通过阻断LDHA-HIF1A通路抑制EC谷氨酰胺代谢,从而抑制EC细胞增殖、侵袭并诱导凋亡。

关键词: 艾司氯胺酮, 谷氨酰胺代谢, 子宫内膜癌, 乳酸脱氢酶A, 缺氧诱导因子1A

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

中图分类号:

R737.33

周广华, 朱腾, 吴玉梅. 艾司氯胺酮通过LDHA-HIF1A通路调节子宫内膜癌中的谷氨酰胺代谢[J]. 医学分子生物学杂志, 2026, 23(2): 107-115.

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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艾司氯胺酮通过LDHA-HIF1A通路调节子宫内膜癌中的谷氨酰胺代谢

Esketamine Regulates Glutaminolysis in Endometrial Cancer via LDHA-HIF1A Pathway

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