脂质代谢重编程在卵巢癌进展和耐药中的作用

doi:10.12280/gjfckx.20250573

国际妇产科学杂志 ›› 2025, Vol. 52 ›› Issue (5): 492-497.doi: 10.12280/gjfckx.20250573

• 妇科肿瘤研究: 综述 • 上一篇下一篇

脂质代谢重编程在卵巢癌进展和耐药中的作用

秦晨, 张玮, 李力^△()

530021 南宁，广西医科大学生命科学研究院，区域性高发肿瘤早期防治研究教育部重点实验室（广西医科大学）（秦晨）；广西壮族自治区肿瘤防治研究所（张玮）；广西医科大学附属肿瘤医院妇瘤科（李力）

收稿日期:2025-05-28 出版日期:2025-10-15 发布日期:2025-10-16
通讯作者: 李力 E-mail:lili@gxmu.edu.cn
作者简介:^△审校者
基金资助:
国家自然科学基金(82160450)

Role of Lipid Metabolism Reprogramming in the Progression and Drug Resistance of Ovarian Cancer

QIN Chen, ZHANG Wei, LI Li^△()

Life Sciences Institute, Guangxi Medical University, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning 530021, China (QIN Chen); Cancer Prevention and Control Research Institute, Guangxi Zhuang Autonomous Region, Nanning 530021, China (ZHANG Wei); Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Nanning 530021, China (LI Li)

Received:2025-05-28 Published:2025-10-15 Online:2025-10-16
Contact: LI Li E-mail:lili@gxmu.edu.cn

摘要/Abstract

摘要：

卵巢癌是致死率最高的妇科恶性肿瘤，其复发和耐药与脂质代谢重编程密切相关。研究表明，脂质代谢异常通过核心代谢酶的异常激活，促进脂肪酸和胆固醇合成，改变细胞膜流动性并驱动致癌信号传导。同时，肿瘤微环境中的腹水、外泌体和免疫细胞通过脂质转运与代谢重塑，进一步增强肿瘤转移和铂类耐药。此外，脂质代谢还与表观遗传修饰和免疫检查点调控相互作用，共同重塑免疫应答并诱导免疫逃逸。这些机制协同作用，维持了癌细胞的存活、侵袭和耐药表型。因此，靶向脂质代谢的关键节点或相关通路不仅有望成为卵巢癌诊断和预后的分子标志物，也可为代谢干预与免疫调节的联合治疗策略提供理论依据，展现出重要的临床转化价值。

关键词: 卵巢肿瘤, 脂类代谢, 肿瘤微环境, 抗药性, 表型

Abstract:

Ovarian cancer is a gynecological malignant tumor with the highest mortality rate, and its recurrence and drug resistance are closely related to lipid metabolism reprogramming. Studies have shown that abnormal lipid metabolism promotes the synthesis of fatty acid and cholesterol through the abnormal activation of core metabolic enzymes, alters the fluidity of the cell membrane, and drives oncogenic signal transduction. Meanwhile, ascites, exosomes, and immune cells in the tumor microenvironment further enhance tumor metastasis and platinum resistance through lipid transport and metabolic remodeling. Moreover, lipid metabolism interacts with epigenetic modifications and immune checkpoint regulation to reshape the immune response and induce immune escape. These mechanisms work together to maintain the survival, invasion, and drug-resistant phenotypes of cancer cells. Therefore, targeting the key nodes or related pathways of lipid metabolism is not only expected to become molecular markers for the diagnosis and prognosis of ovarian cancer, but also provides a theoretical basis for the combined treatment strategy of metabolic intervention and immune regulation, showing important clinical translational value.

Key words: Ovarian neoplasms, Lipid metabolism, Tumor microenvironment, Drug resistance, Phenotype

秦晨, 张玮, 李力. 脂质代谢重编程在卵巢癌进展和耐药中的作用[J]. 国际妇产科学杂志, 2025, 52(5): 492-497.

QIN Chen, ZHANG Wei, LI Li. Role of Lipid Metabolism Reprogramming in the Progression and Drug Resistance of Ovarian Cancer[J]. Journal of International Obstetrics and Gynecology, 2025, 52(5): 492-497.

参考文献 30

[1]	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3):229-263. doi: 10.3322/caac.21834.
[2]	Criscuolo D, Avolio R, Calice G, et al. Cholesterol Homeostasis Modulates Platinum Sensitivity in Human Ovarian Cancer[J]. Cells, 2020, 9(4):828. doi: 10.3390/cells9040828.
[3]	Kopecka J, Trouillas P, Gašparović AČ, et al. Phospholipids and cholesterol: Inducers of cancer multidrug resistance and therapeutic targets[J]. Drug Resist Updat, 2020, 49:100670. doi: 10.1016/j.drup.2019.100670.
[4]	Tan Y, Li J, Zhao G, et al. Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells[J]. Nat Commun, 2022, 13(1):4554. doi: 10.1038/s41467-022-32101-w. pmid: 35931676
[5]	Pavlova NN, Thompson CB. The Emerging Hallmarks of Cancer Metabolism[J]. Cell Metab, 2016, 23(1):27-47. doi: 10.1016/j.cmet.2015.12.006. pmid: 26771115
[6]	Martínez-Reyes I, Chandel NS. Cancer metabolism: looking forward[J]. Nat Rev Cancer, 2021, 21(10):669-680. doi: 10.1038/s41568-021-00378-6. pmid: 34272515
[7]	Bian X, Liu R, Meng Y, et al. Lipid metabolism and cancer[J]. J Exp Med, 2021, 218(1):e20201606. doi: 10.1084/jem.20201606.
[8]	Ji Z, Shen Y, Feng X, et al. Deregulation of Lipid Metabolism: The Critical Factors in Ovarian Cancer[J]. Front Oncol, 2020, 10:593017. doi: 10.3389/fonc.2020.593017.
[9]	Wang Y, Wang Y, Shen L, et al. Prognostic and therapeutic implications of increased ATP citrate lyase expression in human epithelial ovarian cancer[J]. Oncol Rep, 2012, 27(4):1156-1162.doi: 10.3892/or.2012.1638. pmid: 22266777
[10]	Wojnarowicz PM, Breznan A, Arcand SL, et al. Construction of a chromosome 17 transcriptome in serous ovarian cancer identifies differentially expressed genes[J]. Int J Gynecol Cancer, 2008, 18(5):963-975. doi: 10.1111/j.1525-1438.2007.01134.x.
[11]	Palazzolo S, Saorin G, Corona G, et al. A carrier free delivery system of a MAGL inhibitor is effective on ovarian cancer[J]. Eur J Pharm Biopharm, 2024, 203:114397. doi: 10.1016/j.ejpb.2024.114397.
[12]	Wang Y, Hu M, Cao J, et al. ACSL4 and polyunsaturated lipids support metastatic extravasation and colonization[J]. Cell, 2025, 188(2):412-429.e27. doi: 10.1016/j.cell.2024.10.047. pmid: 39591965
[13]	Wu R, Li N, Huang W, et al. Melittin suppresses ovarian cancer growth by regulating SREBP1-mediated lipid metabolism[J]. Phytomedicine, 2025, 137:156367. doi: 10.1016/j.phymed.2025.156367.
[14]	Wu Y, Jia C, Liu W, et al. Sodium citrate targeting Ca²⁺/CAMKK2 pathway exhibits anti-tumor activity through inducing apoptosis and ferroptosis in ovarian cancer[J]. J Adv Res, 2024, 65:89-104. doi: 10.1016/j.jare.2024.04.033.
[15]	Wang H, Luo S, Yin Y, et al. DLAT is involved in ovarian cancer progression by modulating lipid metabolism through the JAK2/STAT5A/SREBP1 signaling pathway[J]. Cancer Cell Int, 2025, 25(1):25. doi: 10.1186/s12935-025-03656-7. pmid: 39871246
[16]	Chen RR, Yung M, Xuan Y, et al. Targeting of lipid metabolism with a metabolic inhibitor cocktail eradicates peritoneal metastases in ovarian cancer cells[J]. Commun Biol, 2019, 2:281. doi: 10.1038/s42003-019-0508-1. pmid: 31372520
[17]	Zhang J, Liu H, Wu Q, et al. Exosomal ANXA2 facilitates ovarian cancer peritoneal metastasis by activating peritoneal mesothelial cells through binding with TLR2[J]. Cell Commun Signal, 2024, 22(1):616. doi: 10.1186/s12964-024-01987-y. pmid: 39709496
[18]	Luo H, She X, Zhang Y, et al. PLIN2 Promotes Lipid Accumulation in Ascites-Associated Macrophages and Ovarian Cancer Progression by HIF1α/SPP1 Signaling[J]. Adv Sci(Weinh), 2025, 12(12):e2411314. doi: 10.1002/advs.202411314.
[19]	Mukherjee A, Chiang CY, Daifotis HA, et al. Adipocyte-Induced FABP4 Expression in Ovarian Cancer Cells Promotes Metastasis and Mediates Carboplatin Resistance[J]. Cancer Res, 2020, 80(8):1748-1761. doi: 10.1158/0008-5472.CAN-19-1999. pmid: 32054768
[20]	Kouba S, Ouldamer L, Garcia C, et al. Lipid metabolism and Calcium signaling in epithelial ovarian cancer[J]. Cell Calcium, 2019, 81:38-50. doi: 10.1016/j.ceca.2019.06.002. pmid: 31200184
[21]	Tang R, Zhu Y, Chen L, et al. Lipid metabolites abnormally expressed in pelvic fluid as potential biomarkers for ovarian cancer: A case-control study[J]. J Proteomics, 2024, 307:105261. doi: 10.1016/j.jprot.2024.105261.
[22]	Feng J, Rouse CD, Taylor L, et al. Regulation of Age-Related Lipid Metabolism in Ovarian Cancer[J]. Int J Mol Sci, 2025, 26(1):320. doi: 10.3390/ijms26010320.
[23]	Lin F, Li X, Wang X, et al. Stanniocalcin 1 promotes metastasis, lipid metabolism and cisplatin chemoresistance via the FOXC2/ITGB6 signaling axis in ovarian cancer[J]. J Exp Clin Cancer Res, 2022, 41(1):129. doi: 10.1186/s13046-022-02315-3. pmid: 35392966
[24]	Xuan Y, Wang H, Yung MM, et al. SCD1/FADS2 fatty acid desaturases equipoise lipid metabolic activity and redox-driven ferroptosis in ascites-derived ovarian cancer cells[J]. Theranostics, 2022, 12(7):3534-3552. doi: 10.7150/thno.70194. pmid: 35547771
[25]	Su YT, Chang WC, Chen L, et al. Ether-Linked Glycerophospholipids Are Potential Chemo-Desensitisers and Are Associated With Overall Survival in Carcinoma Patients[J]. J Cell Mol Med, 2024, 28(24):e70277. doi: 10.1111/jcmm.70277.
[26]	Yi J, Wu M, Zheng Z, et al. Integrated analysis of DNA methylome and transcriptome reveals SFRP1 and LIPG as potential drivers of ovarian cancer metastasis[J]. J Gynecol Oncol, 2023, 34(6):e71. doi: 10.3802/jgo.2023.34.e71. pmid: 37417299
[27]	Gu H, Bock C, Mikkelsen TS, et al. Genome-scale DNA methylation mapping of clinical samples at single-nucleotide resolution[J]. Nat Methods, 2010, 7(2):133-136. doi: 10.1038/nmeth.1414. pmid: 20062050
[28]	Sutton MN, Glazer SE, Al Zaki A, et al. Statins inhibit onco-dimerization of the 4Ig isoform of B7-H3[J]. bioRxiv,2024 Dec 20:2024.12.18.628944. doi: 10.1101/2024.12.18.628944.
[29]	Hwang SM, Awasthi D, Jeong J, et al. Transgelin 2 guards T cell lipid metabolism and antitumour function[J]. Nature, 2024, 635(8040):1010-1018. doi: 10.1038/s41586-024-08071-y.
[30]	Yin ZY, He SM, Zhang XY, et al. Apolipoprotein B100 acts as a tumor suppressor in ovarian cancer via lipid/ER stress axis-induced blockade of autophagy[J]. Acta Pharmacol Sin, 2025, 46(5):1445-1461. doi: 10.1038/s41401-024-01470-x.

脂质代谢重编程在卵巢癌进展和耐药中的作用

Role of Lipid Metabolism Reprogramming in the Progression and Drug Resistance of Ovarian Cancer

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