Research Progress of Glucagon-Like Peptide-1 Receptor Agonist in Endometrial Cancer

doi:10.12280/gjfckx.20241179

Abstract

Abstract:

Endometrial cancer (EC) is one of the most common malignant tumors in the female reproductive system, and its incidence is on the rise globally. Glucagon-like peptide-1 receptor agonist (GLP-1RA) as hypoglycemic drug, has gradually attracted attention for their potential role in the treatment of EC. Existing studies have preliminarily demonstrated that GLP-1RA can regulate the physiological activities of EC by activating multiple signaling pathways such as AMP- activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) and cyclic adenosine monophosphate (cAMP)/protein kinase A(PKA). This further affects apoptosis, autophagy, ferroptosis, and cell cycle arrest of EC cells, and shows the potential to overcome cisplatin chemotherapy resistance in a hyperglycemic environment, thereby inhibiting the survival, migration, and invasion abilities of EC cells. In addition, GLP-1RA can upregulate the expression of glucagon-like peptide-1 receptor (GLP-1R), and changes in the expression level of GLP-1R can be detected in both normal tissues and EC tissues. Therefore, GLP-1RA has potential application value in the treatment of EC. This review summarizes the latest research progress of GLP-1RA in the occurrence and development of EC from the perspectives of key targets, physiological mechanisms, and effects, aiming to provide reference for future research.

Key words: Endometrial neoplasms, Apoptosis, Autophagy, Ferroptosis, Drug resistance, neoplasm, Glucagon-like peptide-1 receptor agonists

JIANG Hao-zhe, SHANG Dan-dan, WANG Shan, WAN Jin-liang. Research Progress of Glucagon-Like Peptide-1 Receptor Agonist in Endometrial Cancer[J]. Journal of International Obstetrics and Gynecology, 2025, 52(5): 486-491.

Figures/Tables 1

References 37

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文献	处理方式	研究类型	正常EC组织中的表达	靶点/通路	作用机制	作用效果
Zhang等^[11]	艾塞那肽	动物实验+ 体外实验	-	AMPK/mTOR	上调p-AMPK，p-AMPK抑制mTOR磷酸化，再通过mTOR上调caspase-3	促进EC细胞凋亡，抑制肿瘤生长
Kanda等^[12]	利拉鲁肽	体外实验	-	AMPK	上调AMPK、p-AMPK和LC3，下调p62	促进细胞凋亡、自噬，抑制癌细胞的生长，阻滞细胞周期
Zhu等^[13]	利拉鲁肽	体外实验	-	AMPK、PR、 p-P70S6K	上调AMPK、PR，下调p-P70S6K	上调孕酮受体表达；与孕酮协同抑制癌细胞增殖
Zhang等^[14]	艾塞那肽	体外实验	-	AMPK、ROS、LDH	上调AMPK、ROS、LDH	减弱高血糖诱导的化疗耐药性；增强凋亡、调控细胞周期效果和细胞毒性
李武等^[15]	①艾塞那肽 ②敲低GLP- 1R基因	体外实验	上调	-	-	①艾塞那肽促进EC细胞增殖；②敲低GLP-1R基因可抑制EC细胞活力
Li等^[16]	过表达GLP- 1R	动物实验+ 体外实验	下调	cAMP/PKA	上调cAMP、PKA	抑制EC细胞的增殖，促进其凋亡；动物实验中肿瘤体积和质量减小
Li等^[17]	①敲除GLP- 1R基因 ②艾塞那肽	体外实验	上调	ROS、SLC7A11、FTH1、GPX4	下调ROS、SLC7A11、FTH1，上调GPX4（应用艾塞那肽则效果相反）	①下调GLP-1R使EC细胞活力、迁移和侵袭能力显著降低，诱导细胞周期阻滞、细胞凋亡和铁死亡；②艾塞那肽上调GLP-1R表达

文献	处理方式	研究类型	正常EC组织中的表达	靶点/通路	作用机制	作用效果
Zhang等^[11]	艾塞那肽	动物实验+ 体外实验	-	AMPK/mTOR	上调p-AMPK，p-AMPK抑制mTOR磷酸化，再通过mTOR上调caspase-3	促进EC细胞凋亡，抑制肿瘤生长
Kanda等^[12]	利拉鲁肽	体外实验	-	AMPK	上调AMPK、p-AMPK和LC3，下调p62	促进细胞凋亡、自噬，抑制癌细胞的生长，阻滞细胞周期
Zhu等^[13]	利拉鲁肽	体外实验	-	AMPK、PR、 p-P70S6K	上调AMPK、PR，下调p-P70S6K	上调孕酮受体表达；与孕酮协同抑制癌细胞增殖
Zhang等^[14]	艾塞那肽	体外实验	-	AMPK、ROS、LDH	上调AMPK、ROS、LDH	减弱高血糖诱导的化疗耐药性；增强凋亡、调控细胞周期效果和细胞毒性
李武等^[15]	①艾塞那肽 ②敲低GLP- 1R基因	体外实验	上调	-	-	①艾塞那肽促进EC细胞增殖；②敲低GLP-1R基因可抑制EC细胞活力
Li等^[16]	过表达GLP- 1R	动物实验+ 体外实验	下调	cAMP/PKA	上调cAMP、PKA	抑制EC细胞的增殖，促进其凋亡；动物实验中肿瘤体积和质量减小
Li等^[17]	①敲除GLP- 1R基因 ②艾塞那肽	体外实验	上调	ROS、SLC7A11、FTH1、GPX4	下调ROS、SLC7A11、FTH1，上调GPX4（应用艾塞那肽则效果相反）	①下调GLP-1R使EC细胞活力、迁移和侵袭能力显著降低，诱导细胞周期阻滞、细胞凋亡和铁死亡；②艾塞那肽上调GLP-1R表达