References
- 1.MAOMAO C,HE L,DIANQIN S,et al.Current cancer burden in China:Epidemiology,etiology,and prevention[J].Cancer Biol Med,2022,19(8):1121-1138.
- 2.MCGLYNN K A,PETRICK J L,GROOPMAN J D.Liver cancer:Progress and priorities[J].Cancer Epidemiol Biomarkers Prev,2024,33(10):1261-1272.
- 3.HUANG P S,WANG L Y,WANG Y W,et al.Evaluation and application of drug resistance by biomarkers in the clinical treatment of liver cancer[J].Cells,2023,12(6):869.
- 4.XUE Y,RUAN Y,WANG Y,et al.Signaling pathways in liver cancer:Pathogenesis and targeted therapy[J].Mol Biomed,2024,5(1):20.
- 5.XU X Y,ZHU Y P,LIU Y Q,et al.Mechanism of treatment of hepatocellular carcinoma with traditional Chinese medicine based on epigenetic regulation:A review [J].Chin J Exp Tradit Med Form,2024,30(23):281-291.
- 6.MA Y N,JIANG X,TANG W,et al.Influence of intermittent fasting on autophagy in the liver[J].Biosci Trends,2023,17(5):335-355.
- 7.XIANG H,ZHANG J,LIN C,et al.Targeting autophagy-related protein kinases for potential therapeutic purpose[J].Acta Pharm Sin B,2020,10(4):569-581.
- 8.PENUGURTI V,MISHRA Y G,MANAVATHI B.AMPK:An odyssey of a metabolic regulator,a tumor suppressor,and now a contextual oncogene[J].Biochim Biophys Acta Rev Cancer,2022,1877(5):188785.
- 9.KHALIL M I,ALI M M,HOLAIL J,et al.Growth or death? Control of cell destiny by mTOR and autophagy pathways[J].Prog Biophys Mol Biol,2023,185:39-55.
- 10.MOSSMANN D,PARK S,HALL M N.mTOR signalling and cellular metabolism are mutual determinants in cancer[J].Nat Rev Cancer,2018,18(12):744-757.
- 11.GE Y,ZHOU M,CHEN C,et al.Role of AMPK mediated pathways in autophagy and aging[J].Biochimie,2022,195:100-113.
- 12.MENG S S,GU H W,ZHANG T,et al.Gradual deterioration of fatty liver disease to liver cancer via inhibition of AMPK signaling pathways involved in energy-dependent disorders,cellular aging,and chronic inflammation[J].Front Oncol,2023,13:1099624.
- 13.CUI J,SHEN H M,LIM L H K.The role of autophagy in liver cancer:Crosstalk in signaling pathways and potential therapeutic targets[J].Pharmaceuticals (Basel),2020,13(12):432.
- 14.LIU G,KUANG S,CAO R,et al.Sorafenib kills liver cancer cells by disrupting SCD1-mediated synthesis of monounsaturated fatty acids via the ATP-AMPK-mTOR-SREBP1 signaling pathway[J].Faseb j,2019,33(9):10089-10103.
- 15.HERNANDEZ G A,PERERA R M.Autophagy in cancer cell remodeling and quality control[J].Mol Cell,2022,82(8):1514-1527.
- 16.MILLER D R,THORBURN A.Autophagy and organelle homeostasis in cancer[J].Dev Cell,2021,56(7):906-918.
- 17.CHAO X,QIAN H,WANG S,et al.Autophagy and liver cancer[J].Clin Mol Hepatol,2020,26(4):606-617.
- 18.RAHMAN M A,RAKIB-UZ-ZAMAN S M,CHAKRABORTI S,et al.Advancements in utilizing natural compounds for modulating autophagy in liver cancer:Molecular mechanisms and therapeutic targets[J].Cells,2024,13(14):1186.
- 19.CAO W,LI J,YANG K,et al.An overview of autophagy:Mechanism,regulation and research progress[J].Bull Cancer,2021,108(3):304-322.
- 20.WANG H,LIU Y,WANG D,et al.The upstream pathway of mTOR-mediated autophagy in liver diseases[J].Cells,2019,8(12):1597.
- 21.WANG Z,SHEN J,CHEN C,et al.FOXA2 plays a critical role in hepatocellular carcinoma progression and lenvatinib-associated drug resistance[J].Biosci Trends,2023,17(2):136-147.
- 22.KASHYAP D,GARG V K,GOEL N.Intrinsic and extrinsic pathways of apoptosis:Role in cancer development and prognosis[J].Adv Protein Chem Struct Biol,2021,125:73-120.
- 23.BORAEI A T A,ELTAMANY E H,ALI I A I,et al.Synthesis of new substituted pyridine derivatives as potent anti-liver cancer agents through apoptosis induction:In vitro,in vivo,and in silico integrated approaches[J].Bioorg Chem,2021,111:104877.
- 24.CARNEIRO B A,EL-DEIRY W S.Targeting apoptosis in cancer therapy[J].Nat Rev Clin Oncol,2020,17(7):395-417.
- 25.XIE G,SUN L,LI Y,et al.Periplocin inhibits the growth of pancreatic cancer by inducing apoptosis via AMPK-mTOR signaling[J].Cancer Med,2021,10(1):325-336.
- 26.ZHENG Y,WANG K,WU C,et al.COTI-2 suppresses the malignancy of bladder cancer by inducing apoptosis via the AMPK-mTOR signaling pathway[J].Iran J Basic Med Sci,2025,28(3):240-246.
- 27.LIU X,HU X,KUANG Y,et al.BCLB,methylated in hepatocellular carcinoma is a starvation stress sensor that induces apoptosis and autophagy through the AMPK-mTOR signaling cascade[J].Cancer Lett,2017,395:63-71.
- 28.VAN NOORDEN C J F,YETKIN-ARIK B,SERRANO MARTINEZ P,et al.New insights in ATP synthesis as therapeutic target in cancer and angiogenic ocular diseases[J].J Histochem Cytochem,2024,72(5):329-352.
- 29.FENG J,LI J,WU L,et al.Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma[J].J Exp Clin Cancer Res,2020,39(1):126.
- 30.DU D,LIU C,QIN M,et al.Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma[J].Acta Pharm Sin B,2022,12(2):558-580.
- 31.WANG B,PU R.Association between glycolysis markers and prognosis of liver cancer:A systematic review and Meta-analysis[J].World J Surg Oncol,2023,21(1):390.
- 32.BOUROUH M,MARIGNANI P A.The tumor suppressor kinase LKB1:Metabolic nexus[J].Front Cell Dev Biol,2022,10:881297.
- 33.ZEB A,KHAN W,UL ISLAM W ,et al.Exploring the anticancer potential of astragalin in triple negative breast cancer cells by attenuating glycolytic pathway through AMPK/mTOR[J].Curr Med Chem,2024,doi:.
- 34.FANG G,ZHANG P,LIU J,et al.Inhibition of GSK-3β activity suppresses HCC malignant phenotype by inhibiting glycolysis via activating AMPK/mTOR signaling[J].Cancer Lett,2019,463:11-26.
- 35.YE H,LIU Y,WU K,et al.AMPK activation overcomes anti-EGFR antibody resistance induced by KRAS mutation in colorectal cancer[J].Cell Commun Signal,2020,18(1):115.
- 36.ZHANG H,YU J,MA L,et al.Reversing multi-drug resistance by polymeric metformin to enhance antitumor efficacy of chemotherapy[J].Int J Pharm,2022,624:121931.
- 37.LI J,WU P W,ZHOU Y,et al.Rage induces hepatocellular carcinoma proliferation and sorafenib resistance by modulating autophagy[J].Cell Death Dis,2018,9(2):225.
- 38.REYES R,WANI N A,GHOSHAL K,et al.Sorafenib and 2-deoxyglucose synergistically inhibit proliferation of both sorafenib-sensitive and -resistant HCC cells by inhibiting ATP production[J].Gene Expr,2017,17(2):129-140.
- 39.CHEKI M,MOSTAFAEI S,HANAFI M G,et al.Radioproteomics modeling of metformin-enhanced radiosensitivity:An animal study[J].Jpn J Radiol,2023,41(11):1265-1274.
- 40.KIM E H,KIM M S,FURUSAWA Y,et al.Metformin enhances the radiosensitivity of human liver cancer cells to γ-rays and carbon ion beams[J].Oncotarget,2016,7(49):80568-80578.
- 41.BATTAGLIA A M,CHIRILLO R,AVERSA I,et al.Ferroptosis and cancer:Mitochondria meet the "iron maiden" cell death[J].Cells,2020,9(6):1505.
- 42.TONG X,TANG R,XIAO M,et al.Targeting cell death pathways for cancer therapy:Recent developments in necroptosis,pyroptosis,ferroptosis,and cuproptosis research[J].J Hematol Oncol,2022,15(1):174.
- 43.ZHANG B,ZHAO J,LIU B,et al.Development and validation of a novel ferroptosis-related gene signature for prognosis and immunotherapy in hepatocellular carcinoma[J].Front Mol Biosci,2022,doi:.
- 44.HAN D,JIANG L,GU X,et al.SIRT3 deficiency is resistant to autophagy-dependent ferroptosis by inhibiting the AMPK/mTOR pathway and promoting GPX4 levels[J].J Cell Physiol,2020,235(11):8839-8851.
- 45.SUN Z,LIU L,LIANG H,et al.Nicotinamide mononucleotide induces autophagy and ferroptosis via AMPK/mTOR pathway in hepatocellular carcinoma[J].Mol Carcinog,2024,63(4):577-588.
- 46.HUANG Y,HONG W,WEI X.The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis[J].J Hematol Oncol,2022,15(1):129.
- 47.LI Z,LIU B,LI C,et al.NRBP2 functions as a tumor suppressor and inhibits epithelial-to-mesenchymal transition in breast cancer[J].Front Oncol,2021,11:634026.
- 48.QUE T,REN B,FAN Y,et al.Capsaicin inhibits the migration,invasion and EMT of renal cancer cells by inducing AMPK/mTOR-mediated autophagy[J].Chem Biol Interact,2022,366:110043.
- 49.SUN Y,LEI B,HUANG Q.SOX18 affects cell viability,migration,invasiveness,and apoptosis in hepatocellular carcinoma (HCC) cells by participating in epithelial-to-mesenchymal transition (EMT) progression and adenosine monophosphate activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)[J].Med Sci Monit,2019,25:6244-6254.
- 50.HEAD S A,SHI W Q,YANG E J,et al.Simultaneous targeting of NPC1 and VDAC1 by itraconazole leads to synergistic inhibition of mTOR signaling and angiogenesis[J].ACS Chem Biol,2017,12(1):174-182.
- 51.FU C,AN N,LIU J,et al.The transcription factor ZFHX3 is crucial for the angiogenic function of hypoxia-inducible factor 1α in liver cancer cells[J].J Biol Chem,2020,295(20):7060-7074.
- 52.WEI H,XU Z,CHEN L,et al.Long non-coding RNA PAARH promotes hepatocellular carcinoma progression and angiogenesis via upregulating HOTTIP and activating HIF-1α/VEGF signaling[J].Cell Death Dis,2022,13(2):102.
- 53.JIANG D,QI Z,XU Z Y,et al.F13B regulates angiogenesis and tumor progression in hepatocellular carcinoma via the HIF-1α/VEGF pathway[J].Biomol Biomed,2024,25(1):189-209.
- 54.LEI H W,CAI J,LI C M,et al.Rapamycin combined with TAE on the growth,metastasis,and prognosis of hepatocellular carcinoma in rat models[J].Ann Hepatol,2018,17(4):645-654.
- 55.PAKRAVAN K,BABASHAH S,SADEGHIZADEH M,et al.MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1α/VEGF signaling axis in breast cancer cells[J].Cell Oncol (Dordr),2017,40(5):457-470.
- 56.LI Y,SUN R,ZOU J,et al.Dual roles of the AMP-activated protein kinase pathway in angiogenesis[J].Cells,2019,8(7):752.
- 57.WEI T,CHENG J,JI Y,et al.Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/Akt/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma[J].Open Life Sci,2024,19(1):20220914.
- 58.KIM S M,HA S E,LEE H J,et al.Sinensetin induces autophagic cell death through p53-Related AMPK/mTOR signaling in hepatocellular carcinoma HepG2 cells[J].Nutrients,2020,12(8):2462.
- 59.YIN X,LI W,ZHANG J,et al.AMPK-mediated metabolic switching is high effective for phytochemical levo-tetrahydropalmatine (l-THP) to reduce hepatocellular carcinoma tumor growth[J].Metabolites,2021,11(12):811.
- 60.HAN B,YU Y Q,YANG Q L,et al.Kaempferol induces autophagic cell death of hepatocellular carcinoma cells via activating AMPK signaling[J].Oncotarget,2017,8(49):86227-86239.
- 61.ZHANG H,SU X,GU L,et al.Colchicine-mediated selective autophagic degradation of HBV core proteins inhibits HBV replication and HBV-related hepatocellular carcinoma progression[J].Cell Death Discov,2024,10(1):352.
- 62.FAN H,JI Y,WANG Y,et al.Anthocyanins from Lycium ruthenicum murray inhibit HepG2 cells growth,metastasis and promote apoptosis and G2/M phase cycle arrest by activating the AMPK/mTOR autophagy pathway[J].Evid Based Complement Alternat Med,2022,2022:9609596.
- 63.CHEN Y L,YEN I C,LIN K T,et al.4-Acetylantrocamol LT3,a new ubiquinone from Antrodia cinnamomea,inhibits hepatocellular carcinoma HepG2 cell growth by targeting YAP/TAZ,mTOR,and Wnt/β-catenin signaling[J].Am J Chin Med,2020,48(5):1243-1261.
- 64.EL-SEWEDY T,SALAMA A F,MOHAMED A E,et al.Hepatocellular carcinoma cells:Activity of amygdalin and sorafenib in targeting AMPK /mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death[J].BMC Complement Med Ther,2023,23(1):329.
- 65.AL-ZAHRANI N S,ZAMZAMI M A,BAGHDADI M A,et al.Regulation of protein-induced apoptosis and autophagy in human hepatocytes treated with metformin and paclitaxel in silico and in vitro[J].Biomedicines,2023,11(10):2688.
- 66.YU H,HAO Z,LIU X,et al.Autophagy blockage and lysosomal dysfunction are involved in diallyl sulfide-induced inhibition of malignant growth in hepatocellular carcinoma cells[J].Environ Toxicol,2023,38(9):2100-2110.
- 67.SHUI L,WANG W,XIE M,et al.Isoquercitrin induces apoptosis and autophagy in hepatocellular carcinoma cells via AMPK/mTOR/p70S6K signaling pathway[J].Aging (Albany NY),2020,12(23):24318-24332.
- 68.KWON H Y,KIM J H,KIM B,et al.Regulation of SIRT1/AMPK axis is critically involved in gallotannin-induced senescence and impaired autophagy leading to cell death in hepatocellular carcinoma cells[J].Arch Toxicol,2018,92(1):241-257.
- 69.LEE Y G,JANG S A,SONG H S,et al.Bakuchiol from Cullen corylifolium and its efficacy on apoptosis and autophagy in HepG2 cells[J].Heliyon,2024,10(23):e40758.
- 70.WU H,QU L,BAI X,et al.Ginsenoside Rk1 induces autophagy-dependent apoptosis in hepatocellular carcinoma by AMPK/mTOR signaling pathway[J].Food Chem Toxicol,2024,186:114587.
- 71.CUI Y Q,LIU Y J,ZHANG F.The suppressive effects of Britannin (Bri) on human liver cancer through inducing apoptosis and autophagy via AMPK activation regulated by ROS[J].Biochem Biophys Res Commun,2018,497(3):916-923.
- 72.WANG P,ZHANG S D,JIAO J,et al.ROS-mediated p53 activation by juglone enhances apoptosis and autophagy in vivo and in vitro[J].Toxicol Appl Pharmacol,2019,379:114647.
- 73.VISHNOI K,KE R,SAINI K S,et al.Berberine represses β-catenin translation involving 4E-BPs in hepatocellular carcinoma cells[J].Mol Pharmacol,2021,99(1):1-16.
- 74.HAN M,GAO H,XIE J,et al.Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cells in vitro and in vivo by activating AMPK signaling pathway[J].Acta Pharmacol Sin,2019,40(5):666-676.
- 75.CHO A R,PARK W Y,LEE H J,et al.Antitumor effect of morusin via g1 arrest and antiglycolysis by AMPK activation in hepatocellular cancer[J].Int J Mol Sci,2021,22(19):10619.
- 76.HUANG H,XUE J,XIE M L,et al.Osthole inhibits GSK-3β/AMPK/mTOR pathway-controlled glycolysis and increases radiosensitivity of subcutaneous transplanted hepatocellular carcinoma in nude mice[J].Strahlenther Onkol,2024,200(5):444-452.
- 77.ZHANG R,WANG N,FAN B,et al.Potentiation of sorafenib's action by berberine via suppression of the mTOR signaling pathway in human hepatoma cells[J].Nutr Cancer,2025,77(4/5):553-565.
- 78.WANG B,MIN W,LIN S,et al.Saikosaponin-d increases radiation-induced apoptosis of hepatoma cells by promoting autophagy via inhibiting mTOR phosphorylation[J].Int J Med Sci,2021,18(6):1465-1473.
- 79.HE L W,LIN C J,ZHUANG L J,et al.Targeting hepatocellular carcinoma:Schisandrin a triggers mitochondrial disruption and ferroptosis[J].Chem Biol Drug Des,2024,104(6):e70010.
- 80.YANG X,XIE J,LIU X,et al.Autophagy induction by xanthoangelol exhibits anti-metastatic activities in hepatocellular carcinoma[J].Cell Biochem Funct,2019,37(3):128-138.
- 81.KIM Y W,JANG E J,KIM C H,et al.Sauchinone exerts anticancer effects by targeting AMPK signaling in hepatocellular carcinoma cells[J].Chem Biol Interact,2017,261:108-117.


