| 603 | 0 | 25 |
| 下载次数 | 被引频次 | 阅读次数 |
肺癌是全球范围内发病率和病死率最高的恶性肿瘤之一。目前现代医学肺癌治疗方案有放疗、化疗、靶向治疗和手术治疗等，但存在复发、转移、耐药等情况，因此寻找新型有效的靶向药物受到人们广泛关注。磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路与肺癌的发生和演变过程关系密切。研究发现，中医药可以通过抑制该信号通路及其相关靶点蛋白调节细胞周期蛋白与凋亡相关蛋白的表达，抑制细胞增殖、迁移和侵袭，促进肿瘤细胞自噬，诱导细胞凋亡等，发挥抗肺癌作用。该文通过参考大量文献，系统阐述了PI3K/Akt/mTOR信号通路的作用机制，以及中医药靶向调控该信号通路治疗肺癌研究现状，包括中药活性成分、中药制剂以及中药复方，旨在为肺癌的新型靶向药物研发提供理论依据。
Abstract：Lung cancer is one of the most common and deadly malignant tumors worldwide. Currently,modern medical treatments for lung cancer include radiotherapy,chemotherapy,targeted therapy,and surgical treatment,but there are issues such as recurrence,metastasis,and drug resistance. Therefore,the search for new and effective targeted drugs has attracted widespread attention. The phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway is closely related to the occurrence and development of lung cancer. Studies have shown that traditional Chinese medicine can regulate the expression of cell cycle proteins and apoptosis-related proteins by inhibiting this signaling pathway and its related target proteins,inhibit cell proliferation,migration,and invasion,promote autophagy in tumor cells,induce cell apoptosis,etc.,and exert anti-lung cancer effects. This article,by referring to a large number of literatures,systematically expounds the mechanism of action of the PI3K/Akt/mTOR signaling pathway and the current research status of targeted regulation of this signaling pathway by traditional Chinese medicine for lung cancer treatment,including active ingredients of traditional Chinese medicine,traditional Chinese medicine preparations,and traditional Chinese medicine combinations,aiming to provide theoretical basis for the development of new targeted drugs for lung cancer.
[1]RASKOVA KAFKOVA L,MIERZWICKA JM,CHAKRABORTY P,et al. NSCLC:from tumorigenesis,immune checkpoint misuse to current and future targeted therapy[J]. Front Immunol,2024,15:1342086.
[2]PENG Y,WANG Y Y,ZHOU C,et al. PI3K/Akt/mTOR pathway and its role in cancer therapeutics:are we making headway ?[J]. Front Oncol,2022,12:819128.
[3]TAN A C. Targeting the PI3K/Akt/mTOR pathway in non-small cell lung cancer(NSCLC)[J]. Thorac Cancer,2020,11(3):511-518.
[4]LIU F R,GAO S,YANG Y X,et al. Antitumor activity of curcumin by modulation of apoptosis and autophagy in human lung cancer A549 cells through inhibiting PI3K/Akt/mTOR pathway[J]. Oncol Rep,2018,39(3):1523-1531.
[5]JIANG L,ZHANG J B,XU Y,et al. Treating non-small cell lung cancer by targeting the PI3K signaling pathway[J]. Chin Med J,2022,135(11):1272-1284.
[6]BILANGES B,POSOR Y,VANHAESEBROECK B. PI3K isoforms in cell signalling and vesicle trafficking[J]. Nat Rev Mol Cell Biol,2019,20(9):515-534.
[7]YU J J,ZHANG L J,PENG J,et al. Dictamnine,a novel c-Met inhibitor,suppresses the proliferation of lung cancer cells by downregulating the PI3K/Akt/mTOR and MAPK signaling pathways[J]. Biochem Pharmacol,2022,195:114864.
[8]HUA H,ZHANG H Y,CHEN J Z,et al. Targeting Akt in cancer for precision therapy[J]. J Hematol Oncol,2021,14(1):128.
[9]HUANG Y H,CHIU L Y,TSENG J S,et al. Attenuation of PI3KAkt-mTOR pathway to reduce cancer stemness on chemoresistant lung cancer cells by shikonin and synergy with BEZ235inhibitor[J]. Int J Mol Sci,2024,25(1):616.
[10]LI J,HU Z Q,YU S Y,et al. CircRPN2 inhibits aerobic glycolysis and metastasis in hepatocellular carcinoma[J].Cancer Res,2022,82(6):1055-1069.
[11]PONNUSAMY L,NATARAJAN SR,MANOHARAN R.MARK2 potentiate aerobic glycolysis-mediated cell growth in breast cancer through regulating mTOR/HIF-1α and p53pathways[J]. J Cell Biochem,2022,123(4):759-771.
[12]QUAN Z H,YANG Y,ZHENG H M,et al. Clinical implications of the interaction between PD-1/PD-L1 and PI3K/Akt/mTOR pathway in progression and treatment of non-small cell lung cancer[J]. J Cancer,2022,13(13):3434-3443.
[13]SONG X L,FAN P D,BANTIKASSEGN A,et al. ERBB3-independent activation of the PI3K pathway in EGFR-mutant lung adenocarcinomas[J]. Cancer Res,2015,75(6):1035-1045.
[14]DENG H,CHEN Y M,LI P J,et al. PI3K/Akt/mTOR pathway,hypoxia,and glucose metabolism:Potential targets to overcome radioresistance in small cell lung cancer[J]. Cancer Pathog Ther,2023,1(1):56-66.
[15]CHENG F W,PENG L M,LUO D. Methyltransferase-like 3promotes the progression of lung cancer via activating PI3K/Akt/mTOR pathway[J]. Clin Exp Pharmacol Physiol,2022,49(7):748-758.
[16]LIN Y,ZHANG L M,DING X F,et al. Relationship between the microRNAs and PI3K/Akt/mTOR axis:Focus on non-small cell lung cancer[J]. Pathol Res Pract,2022,239:154093.
[17]GANESAN K,XU C,WU JM,et al. Ononin inhibits triplenegative breast cancer lung metastasis by targeting the EGFRmediated PI3K/Akt/mTOR pathway[J]. Sci China Life Sci,2024,67(9):1849-1866.
[18]李瑞峰，吕品，李健刚，等. TRIM26通过EGFR/PI3K/Akt/m TOR信号通路调控肺癌细胞增殖、迁移和侵袭[J/OL].解剖科学进展，2025:1-7.(2025-02-19). https：//kns.cnki.net/KCMS/detail/detail.aspx?filename=JPKΧ2025021900D&dbnam e=CJFD&dbcode=CJFQ.
[19]CZYZYK D,YAN WP,MESSING S,et al. Structural insights into isoform-specific RAS-PI3Kα interactions and the role of RAS in PI3Kα activation[J]. Nat Commun,2025,16(1):525.
[20]肖旭阳，杜天宇，周玄，等. miR-184对顺铂耐药肺癌细胞PI3K、Akt和mTOR蛋白表达的影响[J].郑州大学学报（医学版），2022,57(3):344-349.
[21]LU R Q,ZHAO G,YANG Y L,et al. Inhibition of CD133overcomes cisplatin resistance through inhibiting PI3K/Akt/mTOR signaling pathway and autophagy in CD133-positive gastric cancer cells[J]. Technol Cancer Res Treat,2019,18:1533033819864311.
[22]符雷蕾，杨媛媛，刘博，等.中药来源的天然化合物调控自噬机制及靶向治疗研究进展[J].药学学报，2023,58(9):2569-2580.
[23]JHANWAR-UNIYAL M,ZELLER SL,SPIROLLARI E,et al.Discrete mechanistic target of rapamycin signaling pathways,stem cells,and therapeutic targets[J]. Cells,2024,13(5):409.
[24]KARIMI ROSHAN M,SOLTANI A,SOLEIMANI A,et al.Role of Akt and mTOR signaling pathways in the induction of epithelial-mesenchymal transition(EMT)process[J].Biochimie,2019,165:229-234.
[25]TEOH-FITZGERALD ML,FITZGERALD MP,JENSEN TJ,et al. Genetic and epigenetic inactivation of extracellular superoxide dismutase promotes an invasive phenotype in human lung cancer by disrupting ECM homeostasis[J]. Mol Cancer Res,2012,10(1):40-51.
[26]眭玉霞，庄捷，庄敏，等. Delicaflavone通过PI3K/Akt/mTOR通路调控上皮-间质转化抑制吉非替尼耐药肺癌PC-9/GR细胞迁移和侵袭[J].中国临床药理学与治疗学，2022,27(6):614-621.
[27]黄菊. THBS2通过激活PI3K/Akt/mTOR信号通路参与肺癌血管生成拟态的机制研究[D].长春：吉林大学，2024:44-48.
[28]ZHANG Z,YAO L,YANG J H,et al. PI3K/Akt and HIF-1 signaling pathway in hypoxia-ischemia(Review)[J]. Mol Med Rep,2018,18(4):3547-3554.
[29]SHI S,MA B,SUN F D,et al. Theaflavin binds to a druggable pocket of TMEM16A channel and inhibits lung adenocarcinoma cell viability[J]. J Biol Chem,2021,297(3):101016.
[30]段兴隆，张华.茶黄素调节PI3K/Akt/mTOR信号通路对A549细胞增殖凋亡及自噬的影响[J].河北医学，2024,30(9):1473-1478.
[31]AFZAL SM,VAFA A,RASHID S,et al. Amelioration of N,N'-dimethylhydrazine induced colon toxicity by epigallocatechin gallate in Wistar rats[J]. Hum Exp Toxicol,2021,40(9):1558-1571.
[32]任闪闪，刘燕，尚艺婉，等.基于EGFR/PI3K/Akt/mTOR通路探讨表没食子儿茶素-3-没食子酸酯调控非小细胞肺癌细胞周期和凋亡的机制[J].中医学报，2024,39(6):1280-1288.
[33]DABEEK WM,MARRA MV. Dietary quercetin and kaempferol:bioavailability and potential cardiovascular-related bioactivity in humans[J]. Nutrients,2019,11(10):2288.
[34]REN J,LU Y F,QIAN Y H,et al. Recent progress regarding kaempferol for the treatment of various diseases[J]. Exp Ther Med,2019,18(4):2759-2776.
[35]朱志明，周绮纯，王娟娟，等.山柰酚通过Met/PI3K/Akt/m TOR通路诱导非小细胞肺癌NCI-H1650细胞发生自噬进而影响其增殖[J].中国肿瘤生物治疗杂志，2023,30(11):965-972.
[36]BAO H,ZHENG N B,LI Z T,et al. Synergistic effect of tangeretin and atorvastatin for colon cancer combination therapy:targeted delivery of these dual drugs using RGD peptide decorated nanocarriers[J]. Drug Des Devel Ther,2020,14:3057-3068.
[37]GUL HF,ILHAN N,ILHAN N,et al. The combined effect of pomegranate extract and tangeretin on the DMBA-induced breast cancer model[J]. J Nutr Biochem,2021,89:108566.
[38]王赛，王灵杰，李艳丽，等.桔皮素通过调节PI3K/Akt/mTOR信号通路抑制非小细胞肺癌的肿瘤干性[J].中国胸心血管外科临床杂志，2023,30(4):614-621.
[39]曹雪婷.刺五加苷B调节PI3K/Akt/mTOR通路抑制肺癌细胞生长[D].唐山：华北理工大学，2023:27-29.
[40]高寒，徐伟，张宇航，等.基于网络药理学的刺五加总苷抗疲劳作用机制研究[J].中草药，2021,52(2):413-421.
[41]曹雪婷，吴博雅，陈静.刺五加苷B介导PI3K/Akt/mTOR通路诱导肺癌细胞凋亡和自噬[J].中国中药杂志，2023,48(24):6693-6701.
[42]YANG Q,CAI N,CHE D B,et al. Effect of ginsenoside Rg3nanostructured lipid carrier modified by pullulan on promoting absorption and its anti-tumor evaluation in vitro[J]. China J Chin Mater Med,2020,45(21):5184-5192.
[43]CHEN P F,LI X P,YU X,et al. Ginsenoside Rg1 suppresses non-small-cell lung cancer via microRNA-126-PI3K-AktmTOR pathway[J]. Evid Based Complement Alternat Med,2022,2022:1244836.
[44]HONG G J,ZHOU L,HAN X R,et al. Asiatic acid inhibits OVX-induced osteoporosis and osteoclastogenesis Via regulating RANKL-mediated NF-κb and Nfatc1 signaling pathways[J].Front Pharmacol,2020,11:331.
[45]王子健，庄作会，刘春霞.积雪草酸通过调控PI3K/Akt/mTOR信号通路抑制A549细胞的增殖和迁移[J].中国老年学杂志，2021,41(21):4827-4830.
[46]XUE C,LIU S X,HU J,et al. Corydalis saxicola Bunting total alkaloids attenuate paclitaxel-induced peripheral neuropathy through PKCε/p38 MAPK/TRPV1 signaling pathway[J]. Chin Med,2021,16(1):58.
[47]YUAN R,FAN Q M,LIANG X W,et al. Cucurbitacin B inhibits TGF-β1-induced epithelial-mesenchymal transition(EMT)in NSCLC through regulating ROS and PI3K/Akt/mTOR pathways[J]. Chin Med,2022,17:24.
[48]张舒慧，林玉坤，李海云，等.马钱子水煎液对肺癌细胞体内外的抑制作用[J].河南大学学报（医学版），2017,36(4):239-242.
[49]刘宁，谢壮鑫，陈巧巧，等.马钱子碱通过调控PI3K/Akt/m TOR通路对肺腺癌细胞的抑制作用研究[J].湖南中医杂志，2021,37(10):190-195.
[50]迟笑怡，周天，胡凯文.川芎对恶性肿瘤侵袭与转移影响研究进展[J].中医学报，2019,34(3):495-500.
[51]庞皓玥，胡凯文，孙满强，等.川芎嗪联合顺铂通过调控PI3K/Akt/mTOR通路对人肺癌A549细胞侵袭能力及线粒体功能的影响[J].肿瘤预防与治疗，2021,34(3):199-206.
[52]SONG Y,ZHANG Y,DUAN X Y,et al. Pharmacokinetics and tissue distribution of anwuligan in rats after intravenous and intragastric administration by liquid chromatography-mass spectrometry[J]. Molecules,2019,25(1):39.
[53]文婷婷.安五脂素通过调控let-7c-3p/PI3K/Akt/mTOR信号通路抑制非小细胞肺癌发展[D].长春：吉林大学，2021:82-85.
[54]LONG J,LIU Z,HUI L. Anti-tumor effect and mechanistic study of elemene on pancreatic carcinoma[J]. BMC Complement Altern Med,2019,19(1):133.
[55]LI Y L,WANG T T,SUN Y J,et al. p53-mediated PI3K/Akt/mTOR pathway played a role in PtoxDpt-induced EMT inhibition in liver cancer cell lines[J]. Oxid Med Cell Longev,2019,2019:2531493.
[56]CHENG G Y,LI L,LI Q J,et al. β-elemene suppresses tumor metabolism and stem cell-like properties of non-small cell lung cancer cells by regulating PI3K/Akt/mTOR signaling[J]. Am J Cancer Res,2022,12(4):1535-1555.
[57]桂越蓉，王烁，董军，等.康艾注射液辅助治疗肺癌化疗相关性癌因性疲乏的Meta分析及GRADE评价[J].中医肿瘤学杂志，2023,5(6):108-116.
[58]关念波，毛启远，祁鑫，等.康艾注射液调控调节性T细胞抑制肺癌荷瘤小鼠的作用研究[J].世界中医药，2024,19(21):3296-3304.
[59]吕佳璐，周欢，刘文俊，等.康艾注射液通过抑制PI3K/Akt/m TOR信号通路诱导细胞周期阻滞及自噬性死亡改善A549/DDP细胞顺铂耐药性的研究[J].世界科学技术-中医药现代化，2024,26(12):3127-3135.
[60]卢会琴，柳星，祝永福，等.复方守宫散对非小细胞肺癌患者免疫功能及肺功能的疗效研究[J].安徽医专学报，2024,23(5):18-20.
[61]张良军，蔡琪，黄璟，等.复方守宫散含药血清对PI3K/Akt/m TOR通路介导的小鼠非小细胞肺癌细胞增殖、凋亡的影响[J].中国老年学杂志，2024,44(12):3015-3020.
[62]千维娜，李治，李仁廷，等.培元抗癌汤对人乳腺癌MDAMB-231细胞裸鼠移植瘤生长及细胞凋亡的影响[J].广西医学，2020,42(15):1989-1994.
[63]吴昭利，唐星，李仁廷，等.培元抗癌汤加减对晚期结肠癌脾肾亏虚证患者血浆VEGF、CA724、TGF-β1及肠黏膜屏障功能的影响[J].陕西中医，2021,42(3):315-318.
[64]司海龙，陈玉，苟涛，等.培元抗癌汤通过PI3K-Akt-mTOR信号通路调节Lewis肺癌自噬抑制肿瘤生长和转移的实验研究[J].北京中医药大学学报，2021,44(8):722-728.
[65]杨从影，易剑峰，包梅，等.基于网络药理学探究参麦注射液抗肺癌的扶正-祛邪机制[J].中成药，2020,42(4):1055-1061.
[66]孙冶. miRNA-21调控PI3K/Akt/mTOR信号通路抑制肿瘤细胞糖酵解改善NSCLC顺铂耐药及参麦注射液干预机制的研究[D].沈阳：辽宁中医药大学，2021:96-98.
[67]FENG Z,FENG Z Y,HAN J,et al. Antinociceptive effects of Shenling Baizhu through PI3K-Akt-mTOR signaling pathway in a mouse model of bone metastasis with small-cell lung cancer[J]. Evid Based Complement Alternat Med,2020,2020:4121483.
[68]靳银霞，梁建庆，李尚，等.基于JAK2/STAT3通路探讨归芪益元膏联合顺铂对Lewis肺癌小鼠的抑瘤作用[J].中成药，2025,47(2):573-578.
[69]袁超，孔思琪，梁建庆，等.基于PI3K/Akt/mTOR信号通路探讨归芪益元膏联合顺铂治疗Lewis肺癌的作用[J].中国临床药理学杂志，2024,40(10):1424-1428.
[70]刘冬静，蒋时红，吴耀松，等.六君子汤在肿瘤疾病的应用及疗效机制的研究进展[J].中国中医药现代远程教育，2020,18(5):132-134.
[71]孟丹华，李晨旭，尚艺婉，等.六君子汤治疗恶性肿瘤的研究进展[J].时珍国医国药，2020,31(1):172-174.
[72]吴心语，李和根，廉杰，等. PI3K/Akt/mTOR信号通路在六君子汤含药血清诱导人肺癌细胞A549氧化损伤中作用研究[J].中药材，2022,45(9):2223-2227.
[73]张梦凡.张林军运用桂枝去芍药加麻黄附子细辛汤加减治疗肿瘤的经验[J].中医临床研究，2020,12(24):3-5.
[74]李亮，陈昱丞，王强，等.麻黄附子细辛汤对阳虚型非小细胞肺癌小鼠PI3K/Akt/mTOR信号通路的影响[J].现代中医药，2022,42(2):43-48.
[75]尹全金，王岩，徐磊，等.扶正抑瘤汤对原发性肝癌根治切除术患者术后复发及血管肿瘤标志物水平的影响观察[J].辽宁中医杂志，2022,49(8):133-135.
[76]孟东雪，郭玉荣，罗斌军，等.扶正抑瘤汤通过PI3K/Akt/mTOR信号通路抑制非小细胞肺癌增殖、凋亡及自噬[J].中国癌症防治杂志，2021,13(2):177-182.
基本信息:
DOI：10.13194/j.issn.1673-842X.2026.05.032
中图分类号:R273
引用信息:
[1]谷冰冰,孟泳.中医药调控PI3K/Akt/mTOR信号通路抗肺癌研究进展[J].辽宁中医药大学学报,2026,28(05):209-215.DOI:10.13194/j.issn.1673-842X.2026.05.032.
基金信息:
国家科技重大专项(2024ZD0522902); 河南省高等学校重点科研项目(24A360011); 河南省中医药科学研究专项课题(2023ZY3008); 河南省疫情防控应急科研攻关项目(221111311900)
2025-07-22
2025-07-22
2025-07-22