基于脂质代谢重编程探讨中药防治肝细胞癌的研究进展
1.广西中医药大学研究生院,广西 南宁 530200;
2.柳州市中医医院/柳州市壮医医院,广西 柳州 545001;
3.桂林市中医医院,广西 桂林 541002收稿日期: 2025-01-02
修回日期: 2025-01-20
录用日期: 2025-03-14
网络出版日期: 2025-07-23
基金资助
国家自然科学基金资助项目(82060856、82460958);广西中医药优秀人才研修项目(2023年)
Research Progress on Prevention and Treatment of Hepatocellular Carcinoma with Traditional Chinese Medicine Based on Reprogramming of Lipid Metabolism
Received date: 2025-01-02
Revised date: 2025-01-20
Accepted date: 2025-03-14
Online published: 2025-07-23
肝细胞癌是我国高发病率、死亡率的恶性肿瘤之一,高度依赖不同的代谢途径来维持其生存、侵袭和转移。肝脏作为人体主要的代谢器官,在脂质代谢重编程中起着重要作用。了解肝癌脂质代谢重编程规律,以及如何通过调节脂质代谢以破坏肿瘤生长微环境,有助于更有针对性地治疗肝细胞癌。近年来,关于肝细胞癌脂质代谢重编程相关因子、通路及中药干预肝细胞癌发生发展的研究越来越多,本研究通过对近年来国内外关于肝细胞癌脂质代谢重编程及中药防治肝细胞癌作用机制的研究进展进行论述,以期为肝细胞癌的防治提供策略。
关键词: 肝细胞癌;脂质代谢重编程;中药
卢燕文
,
斯韬
,
黄丽银
.
基于脂质代谢重编程探讨中药防治肝细胞癌的研究进展
Hepatocellular carcinoma is one of the malignant tumors with high morbidity and mortality in China, and is highly dependent on different metabolic pathways for its survival, invasion and metastasis. As a major metabolic organ in the human body, the liver plays an important role in lipid metabolic reprogramming. In-depth understanding of the lipid metabolism reprogramming rules of hepatocellular carcinoma and how to regulate hepatic lipid metabolism in order to disrupt the microenvironment of tumor growth can help to treat hepatocellular carcinoma in a more targeted manner. In recent years, more and more studies have been conducted on the factors and pathways related to lipid metabolic reprogramming in hepatocellular carcinoma and the intervention of traditional Chinese medicine in the development of hepatocellular carcinoma. This sutdy discusses the research progress of lipid metabolic reprogramming in hepatocellular carcinoma and the mechanism of traditional Chinese medicine preventing and controlling hepatocellular carcinoma at home and abroad in recent years, with the aim of providing strategies for the prevention and treatment of hepatocellular carcinoma.
[1] Mossmann D, Müller C, Park S, et al. Arginine reprograms metabolism in liver cancer via RBM39[J].Cell,2023,186(23):5068-5083.
[2] Gao W, Wang J, Xu Y, et al. Research progress in the metabolic reprogramming of hepatocellular carcinoma (Review)[J].Mol Med Rep,2024,30(1):131.
[3] Zhang J, Zhang Z, Wu Z, et al. The switch triggering the invasion process: Lipid metabolism in the metastasis of hepatocellular carcinoma[J].Chin Med J (Engl),2024,137(11):1271-1284.
[4] Feng XC, Liu FC, Chen WY, et al. Lipid metabolism of hepatocellular carcinoma impacts targeted therapy and immunotherapy[J].World J Gastrointest Oncol,2023,15(4):617-631.
[5] Lu M, Wu Y, Xia M, et al. The role of metabolic reprogramming in liver cancer and its clinical perspectives[J].Front Oncol,2024,14:1454161.
[6] Hu B, Lin JZ, Yang XB, et al. Aberrant lipid metabolism in hepatocellular carcinoma cells as well as immune microenvironment: a review[J].Cell Prolif,2020,53(3):e12772.
[7] Cassim S, Raymond VA, Dehbidi-Assadzadeh L, et al. Metabolic reprogramming enables hepatocarcinoma cells to efficiently adapt and survive to a nutrient-restricted microenvironment[J].Cell Cycle,2018,17(7):903-916.
[8] 徐喆,袁克非.脂质代谢重编程与肝癌应激[J].四川大学学报(医学版),2021,52(4):561-565.
[9] Fujiwara N, Nakagawa H, Enooku K, et al. CPT2 downregulation adapts HCC to lipid-rich environment and promotes carcinogenesis via acylcarnitine accumulation in obesity[J].Gut,2018,67(8):1493-1504.
[10] Zhao J, Lee K, Toh HC, et al. Unravelling the role of obesity and lipids during tumor progression[J]. Front Pharmacol,2023,14:1163160.
[11] Yang J, He J, Feng Y, et al. Obesity contributes to hepatocellular carcinoma development via immunosuppressive microenvironment remodeling[J].Front Immunol,2023,14:1166440.
[12] Bi Y, Ying X, Chen W, et al. Glycerophospholipid-driven lipid metabolic reprogramming as a common key mechanism in the progression of human primary hepatocellular carcinoma and cholangiocarcinoma[J].Lipids Health Dis,2024,23(1):326.
[13] Nakagawa H, Hayata Y, Kawamura S, et al. Lipid metabolic reprogramming in hepatocellular carcinoma[J].Cancers (Basel),2018,10(11):447.
[14] Liu HH, Xu Y, Li CJ, et al. An SCD1-dependent mechanoresponsive pathway promotes HCC invasion and metastasis through lipid metabolic reprogramming[J].Mol Ther,2022,30(7):2554-2567.
[15] Rudalska R, Harbig J, Snaebjornsson MT, et al. LXRα activation and Raf inhibition trigger lethal lipotoxicity in liver cancer[J].Nat Cancer,2021,2(2):201-217.
[16] Chen J, Ding C, Chen Y, et al. ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via c-Myc/SREBP1 pathway[J].Cancer Lett,2021,502:154-165.
[17] Su F, Koeberle A. Regulation and targeting of SREBP-1 in hepatocellular carcinoma[J].Cancer Metastasis Rev,2024,43(2):673-708.
[18] Ma APY, Yeung CLS. Suppression of ACADM-mediated fatty acid oxidation promotes hepatocellular carcinoma via aberrant CAV1/SREBP1 signaling[J].Cancer Res,2021,81(13):3679-3692.
[19] He XL, Guo HJ, Lei YR, et al. NAMPT promotes the malignant progression of HBV-associated hepatocellular carcinoma through activation of SREBP1-mediated lipogenesis[J].FASEB J,2024,38(2):e23444.
[20] Yao H, Tao X, Xu L, et al. Dioscin alleviates non-alcoholic fatty liver disease through adjusting lipid metabolism via SIRT1/AMPK signaling pathway[J].Pharmacol Res,2018,131:51-60.
[21] Zhu X, Bian H, Wang L, et al. Berberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway[J].Free Radic Biol Med,2019,141:192-204.
[22] Yang L, Yu S, Yang Y, et al. Berberine improves liver injury induced glucose and lipid metabolic disorders via alleviating ER stress of hepatocytes and modulating gut microbiota in mice[J].Bioorg Med Chem,2022,55:116598.
[23] Meng H, Shen M, Li J, et al. Novel SREBP1 inhibitor cinobufotalin suppresses proliferation of hepatocellular carcinoma by targeting lipogenesis[J].Eur J Pharmacol,2021,906:174280.
[24] Wang M, Li Y, Li S, et al. Cinobufacini injection delays hepatocellular carcinoma progression by regulating lipid metabolism via SREBP1 signaling pathway and affecting macrophage polarization[J].J Ethnopharmacol,2024,321:117472.
[25] Fan Q, Xu F, Liang B, et al. The anti-obesity effect of traditional Chinese medicine on lipid metabolism[J].Front Pharmacol,2021,12:696603.
[26] Peng L, Yan Q, Chen Z, et al. Research progress on the role of cholesterol in hepatocellular carcinoma[J].Eur J Pharmacol,2023,938:175410.
[27] Zhang X, Coker OO, Chu ES, et al. Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites[J].Gut,2021,70(4):761-774.
[28] Alannan M, Fayyad-Kazan H, Trézéguet V, et al. Targeting lipid metabolism in liver cancer[J].Biochemistry,2020,59(41):3951-3964.
[29] Jiang N, Xie B, Xiao W, et al. Fatty acid oxidation fuels glioblastoma radioresistance with CD47-mediated immune evasion[J].Nat Commun,2022,13(1):1511.
[30] Liao J, Xie X, Wang N, et al. Formononetin promotes fatty acid β-oxidation to treat non-alcoholic steatohepatitis through SIRT1/PGC-1α/PPARα pathway[J].Phytomedicine,2024,124:155285.
[31] 曾璐. 基于肝脂肪变性HepG2细胞模型探讨护肝清脂片主要成分对脂质代谢的影响及可能机制[D].南方医科大学, 2015.
[32] Li X, Yu H, Gong Y, et al. Fuzheng xiaozheng prescription relieves rat hepatocellular carcinoma through improving anti-inflammation capacity and regulating lipid related metabolisms[J].J Ethnopharmacol,2022,284:114801.
[33] Ellis H, Ma CX. PI3K inhibitors in breast cancer therapy[J].Curr Oncol Rep,2019,21(12):110.
[34] Tian LY, Smit DJ, Jücker M. The role of PI3K/AKT/mTOR signaling in hepatocellular carcinoma metabolism[J].Int J Mol Sci,2023,24(3):2652.
[35] Liu W, Zheng L, Zhang R, et al. Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma[J].Mol Cancer,2022,21(1):72.
[36] 王金叶. 小豆蔻明抑制CYP1B1调控脂质代谢抑制肝癌细胞增殖的机制研究[D].福建医科大学,2022.
[37] Li S, Hao L, Deng J, et al. Coptidis rhizoma and evodiae fructus against lipid droplet deposition in nonalcoholic fatty liver disease-related liver cancer by AKT[J].Chem Biol Drug Des,2023,102(4):828-842.
[38] 杨芳明,肖准,陈晓琦,等.基于脂质代谢异常探讨“痰浊”理论在肝细胞癌微环境中的生物学内涵[J].临床肝胆病杂志,2023,39(2):432-438.
[39] 尹帅涛,朱依谆.中药提取物对NAFLD作用的研究进展[J].广东化工,2023,50(8):95-97.
[40] Xu H, Yuan M, Niu K, et al. Involvement of Bile acid metabolism and gut microbiota in the amelioration of experimental metabolism-associated fatty liver disease by nobiletin[J].Molecules,2024,29(5):976.
[41] 刘康. 钩藤碱激活脂肪酶改善肝脏脂质代谢紊乱的作用研究[D].广西大学,2023.
[42] Huang F, Zheng X, Ma X, et al. Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism[J].Nat Commun, 2019,10(1):4971.
[43] Zhang SZ, Liang PP, Feng YN, et al. Therapeutic potential and research progress of diosgenin for lipid metabolism diseases[J].Drug Dev Res,2022, 83(8):1725-1738.
[44] Liu YT, Lai YH, Lin HH, et al. Lotus seedpod extracts reduced lipid accumulation and lipotoxicity in hepatocytes[J].Nutrients,2019,11(12):2895.
[45] Xue X, Quan Y, Gong L, et al. A review of the processed polygonum multiflorum (Thunb.) for hepatoprotection: Clinical use, pharmacology and toxicology[J].J Ethnopharmacol,2020,261:113121.
[46] Arora I, Sharma M, Tollefsbol TO. Combinatorial epigenetics impact of polyphenols and phytochemicals in cancer prevention and therapy[J].Int J Mol Sci,2019,20(18):4567.
[47] Wong TL, Strandberg KR, Croley Cr, et al. Pomegranate bioactive constituents target multiple oncogenic and oncosuppressive signaling for cancer prevention and intervention[J]. Semin Cancer Biol,2021,73:265-293.
[48] Cheng KC, Wang CJ, Chang YC, et al. Mulberry fruits extracts induce apoptosis and autophagy of liver cancer cell and prevent hepatocarcinogenesis in vivo[J]. J Food Drug Anal,2020,28(1):84-93.
[49] Li S, Yin S, Ding H, et al. Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention[J].Cell Prolif,2023,56(1):e13346.
[50] Zhang H, Dai Q, Zeng M, et al. Investigating the metabolic level of endogenous and exogenous substances on the intervention of traditional Chinese medicine Fuzheng Yiliu decoction in a rat orthotopic liver cancer model[J].Cancer Manag Res,2022,14:2785-2801.
[51] Cui H, Li Y, Wang Y, et al. Da-Chai-Hu decoction ameliorates high fat diet-induced nonalcoholic fatty liver disease through remodeling the gut microbiota and modulating the serum metabolism[J].Front Pharmacol,2020,11:584090.
[52] Zhong Y, Li J, Zhu X, et al. A comprehensive review of bupleuri radix and its bioactive components: with a major focus on treating chronic liver diseases[J].J Ethnopharmacol,2024,330:118244.
[53] Wu X, Pan J, Yu JJ, et al. DiDang decoction improves mitochondrial function and lipid metabolism via the HIF-1 signaling pathway to treat atherosclerosis and hyperlipidemia[J].J Ethnopharmacol,2023,308:116289.
[54] 宁迪敏.生物钟基因PER1调节脂质代谢对西黄丸抗肝癌效应的影响[D].湖南中医药大学,2022.
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