国际生殖健康/计划生育杂志 ›› 2024, Vol. 43 ›› Issue (1): 79-82.doi: 10.12280/gjszjk.20230328

• 综述 • 上一篇    下一篇

脂肪酸合酶及其抑制剂在子宫内膜癌中的研究进展

冯雅茹, 李雪, 张慧英()   

  1. 300052 天津医科大学总医院妇产科,天津市女性生殖健康与优生重点实验室
  • 收稿日期:2023-08-04 出版日期:2024-01-15 发布日期:2024-01-31
  • 通讯作者: 张慧英,E-mail:huiying_zhang2020@126.com

Fatty Acid Synthase and Its Inhibitors in Endometrial Cancer

FENG Ya-ru, LI Xue, ZHANG Hui-ying()   

  1. Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital, Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin 300052, China
  • Received:2023-08-04 Published:2024-01-15 Online:2024-01-31

摘要:

脂肪酸合酶(fatty acid synthase,FASN)是脂肪酸合成的关键酶,可催化脂质从头合成。正常组织中的脂肪酸大多来源于食物,而在子宫内膜癌细胞中脂肪酸依赖于脂质的从头合成。既往研究表明,FASN的表达与子宫内膜癌的发生、发展及预后不良相关,FASN的过表达与丝裂原细胞外激酶(mitogen extracellular kinase,MEK)/细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)/丝裂原激活的蛋白激酶(mitogen-activated protein kinase,MAPK)和磷脂酰肌醇3激酶(phosphoinositide 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号转导通路相关。因此,特异性阻断FASN的活性可显著抑制肿瘤细胞的生长和增殖。综述子宫内膜癌中FASN的作用机制、FASN抑制剂(如C75、C93、奥利司他等)在子宫内膜癌或其他肿瘤中的研究进展,旨在为子宫内膜肿瘤的治疗提供新思路。

关键词: 脂肪酸合成酶, 酶抑制剂, 治疗, 预后, 子宫内膜肿瘤

Abstract:

Fatty acid synthase (FASN) is a key enzyme in the fatty acid synthesis that catalyzes the de novo synthesis of lipids. Most of the fatty acids are of food origin in normal tissues, while fatty acids are dependent on the de novo synthesis of lipids in endometrial cancer cells. Previous studies have shown that FASN expression is associated with the development, progression and poor prognosis of endometrial malignancies. The overexpression of FASN is correlated with mitogen extracellular kinase (MEK)/ extracellular signal-regulated kinase (ERK)/ mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathways. Specific blockade of its activity can significantly inhibit the growth and proliferation of tumor cells. We review the action of FASN and mechanism in endometrial malignancies and the progress of FASN inhibitors such as C75, C93, orlistat and so on, in endometrial cancer or other tumors, with the aim of providing new ideas for the treatment of endometrial tumors.

Key words: Fatty acid synthases, Enzyme inhibitors, Therapy, Prognosis, Endometrial neoplasms