浏览全部资源
扫码关注微信
1.黑龙江中医药大学,哈尔滨 150040
2.黑龙江中医药大学 附属第一医院,哈尔滨 150040
3.南方医科大学 深圳医院,广东 深圳 518101
Published:20 August 2023,
Published Online:02 February 2023,
Received:19 December 2022,
扫 描 看 全 文
耿雪,迟文成,林霄月等.NF-κB信号通路调控肺癌的机制及中医药干预研究进展[J].中国实验方剂学杂志,2023,29(16):207-216.
GENG Xue,CHI Wencheng,LIN Xiaoyue,et al.Mechanism of NF-κB Signaling Pathway in Regulating Lung Cancer and Intervention of Traditional Chinese Medicine: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(16):207-216.
耿雪,迟文成,林霄月等.NF-κB信号通路调控肺癌的机制及中医药干预研究进展[J].中国实验方剂学杂志,2023,29(16):207-216. DOI: 10.13422/j.cnki.syfjx.20230629.
GENG Xue,CHI Wencheng,LIN Xiaoyue,et al.Mechanism of NF-κB Signaling Pathway in Regulating Lung Cancer and Intervention of Traditional Chinese Medicine: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(16):207-216. DOI: 10.13422/j.cnki.syfjx.20230629.
肺癌是癌症相关死亡的主要原因,肺癌的标准治疗在包括手术、放疗、化疗、靶向治疗、免疫治疗等方面取得了显著的临床效果,但目前可用的治疗策略仍无法治愈。由于绝大多数肺癌患者发现时已为晚期,通常失去手术机会,多以放化疗为主要手段。然而,放化疗带来的不良反应限制了他们的效果和应用,并且对患者正常组织造成的损害通常比对肿瘤的损害更为严重。当前,中药以其独特的辨证体系、灵活的配伍和安全有效的特点已被用作抗癌联合疗法的一部分,中药复方和中药单体的多成分和多靶点性可同时调控多条通路。研究发现,在众多调控肺癌的通路中,核转录因子-
κ
B(NF-
κ
B)信号通路具有诱导细胞转录的功能,是肺癌发生和发展的主要通路之一,在肺癌中能够特异性地调控炎症反应,细胞增殖、凋亡、侵袭和转移,新生血管生成及多药耐药性等。中药复方和中药单体能够通过调控NF-
κ
B信号通路抑制肺癌细胞增殖、侵袭和转移,诱导肺癌细胞凋亡和自噬,抑制血管生成,调控免疫功能及治疗多药耐药,从而起到干预肺癌的作用。然而,国内外尚未有对此进行系统整理与阐述的文献研究。因此,对NF-
κ
B信号通路调控肺癌的机制进行系统阐述并总结中药基于NF-
κ
B信号通路干预肺癌的研究进展,以期为肺癌治疗药物的临床应用和新药研发提供参考。
Lung cancer is the leading cause of cancer-related deaths, and standard treatments for lung cancer, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, have shown significant clinical effects. However, current available treatment strategies are still unable to cure the disease. Since the majority of lung cancer patients are diagnosed at an advanced stage, surgical options are often lost, and the primary approach is typically a combination of radiotherapy and chemotherapy. However, the adverse reactions associated with these treatments limit their effectiveness and application, and the damage caused to normal tissues is often more severe than that inflicted on the tumor. Currently, traditional Chinese medicine (TCM) has been used as part of combination therapy for cancer treatment due to its unique system of syndrome differentiation, flexible compatibility, and safety and efficacy. TCM prescriptions and single drugs with multiple components and targets can simultaneously regulate multiple pathways. As reported, among numerous pathways involved in the regulation of lung cancer, the nuclear factor-
κ
B (NF-
κ
B) signaling pathway plays a key role in inducing cell transcription and is one of the main pathways involved in the occurrence and development of lung cancer. It can specifically regulate inflammatory responses, cell proliferation, apoptosis, invasion and metastasis, angiogenesis, and multidrug resistance in lung cancer. TCM prescriptions and single drugs can inhibit lung cancer cell proliferation, invasion, and metastasis, induce apoptosis and autophagy in lung cancer cells, suppress angiogenesis, regulate immune function, and treat multidrug resistance by regulating the NF-
κ
B signaling pathway. Therefore, they play a role in intervening in lung cancer. However, there is currently a lack of systematic literature research that comprehensively summarizes and elucidates these aspects in China and abroad. Therefore, it is important to provide a systematic elucidation of the mechanism underlying the regulation of the NF-
κ
B signaling pathway in lung cancer and review TCM interventions in lung cancer based on the NF-
κ
B signaling pathway. This study is expected to provide references for the clinical application of lung cancer therapeutic drugs and the development of new drugs.
核转录因子-κB信号通路肺癌中医药研究进展
nuclear factor-kappa Bsignaling pathwaylung cancertraditional Chinese medicineresearch progress
CAO M, CHEN W. Epidemiology of lung cancer in China[J]. Thorac Cancer,2019,10(1):3-7.
ZHANG L, LI H, ZHANG F, et al. CAR-T immunotherapy and non-small cell lung cancer: Bottleneck and dawn[J]. Chin J Lung Cancer,2020,23(10):916-920.
迟文成,耿雪,姜家康,等.中西医结合治疗肿瘤化疗后不良反应的研究进展[J].实用临床医药杂志,2022,26(8):126-130,136.
YE L, JIA Y, JI K, et al. Traditional Chinese medicine in the prevention and treatment of cancer and cancer metastasis (Review)[J]. Oncol Lett,2015,10(3):1240-1250.
王蕾,王雅娟,贺增洋,等.基于TLR4/NF-κB通路探讨石斛多糖改善CSE诱导的人支气管上皮细胞炎性损伤[J].中国实验方剂学杂志,2023,doi:10.13422/j.cnki.syfjx.20230805http://dx.doi.org/10.13422/j.cnki.syfjx.20230805.
LI M, LIU P, WANG B, et al. Inhibition of nuclear factor kappa B as a therapeutic target for lung cancer[J]. Altern Ther Health Med,2022,28(1):44-51.
BONIZZI G, KARIN M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity[J]. Trends Immunol,2004,25(6):280-288.
OECKINGHAUS A, GHOSH S. The NF-kappaB family of transcription factors and its regulation[J]. Cold Spring Harb Perspect Biol,2009,1(4):a000034.
SENFTLEBEN U, CAO Y, XIAO G, et al. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway[J]. Science,2001,293(5534):1495-1499.
VALLABHAPURAPU S, KARIN M. Regulation and function of NF-kappaB transcription factors in the immune system[J]. Annu Rev Immunol, 2009,27:693-733.
DIMITRAKOPOULOS F D, KOTTOROU A E, KALOFONOU M, et al. The fire within: NF-κB involvement in non-small cell lung cancer[J]. Cancer Res,2020,80(19):4025-4036.
BEN-NERIAH Y, KARIN M. Inflammation meets cancer, with NF-κB as the matchmaker[J]. Nat Immunol, 2011,12(8):715-723.
XIA L, TAN S, ZHOU Y, et al. Role of the NF-κB signaling pathway in cancer[J]. Onco Targets Ther, 2018,11:2063-2073.
ZAYNAGETDINOV R, STATHOPOULOS G T, SHERRILL T P, et al. Epithelial nuclear factor-κB signaling promotes lung carcinogenesis via recruitment of regulatory T lymphocytes[J]. Oncogene,2012,31(26):3164-3176.
STATHOPOULOS G T, SHERRILL T P, CHENG D S, et al. Epithelial NF-kappaB activation promotes urethane-induced lung carcinogenesis[J]. Proc Natl Acad Sci USA,2007,104(47):18514-18519.
GUUTTRIDGE D C, ALBANESE C, REUTHER J Y, et al. NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1[J]. Mol Cell Biol,1999,19(8):5785-5799.
WANG X, LIU X, YANG Y, et al. Cyclin D1 mediated by the nuclear translocation of nuclear factor kappa B exerts an oncogenic role in lung cancer[J]. Bioengineered,2022,13(3):6866-6879.
STATHOPOULO G T, SHERRILL T P, HAN W, et al. Host nuclear factor-kappaB activation potentiates lung cancer metastasis[J]. Mol Cancer Res,2008,6(3):364-371.
CAI Z, TCHOU-WONG K M, ROM W N. NF-kappaB in lung tumorigenesis[J]. Cancers (Basel),2011,3(4):4258-4268.
MIN C, EDDY S F, SHERR D H, et al. NF-kappaB and epithelial to mesenchymal transition of cancer[J]. J Cell Biochem,2008,104(3):733-744.
HUANG C Y, FONG Y C, LEE C Y, et al. CCL5 increases lung cancer migration via PI3K, Akt and NF-kappaB pathways[J]. Biochem Pharmacol,2009,77(5):794-803.
KUCHARCZAK J, SIMMONS M J, FAN Y, et al. To be, or not to be: NF-kappaB is the answer-role of Rel/NF-kappaB in the regulation of apoptosis[J]. Oncogene,2003,22(56):8961-8982.
DENLINGER C E, RUNDALL B K, JONES D R. Modulation of antiapoptotic cell signaling pathways in non-small cell lung cancer: The role of NF-kappaB[J]. Semin Thorac Cardiovasc Surg,2004,16(1):28-39.
HE H, XU C, ZHENG L, et al. Polyphyllin Ⅶ induces apoptotic cell death via inhibition of the PI3K/Akt and NF-κB pathways in A549 human lung cancer cells[J]. Mol Med Rep,2020,21(2):597-606.
BATRA R K, LIN Y, SHARMA S, et al. Non-small cell lung cancer-derived soluble mediators enhance apoptosis in activated T lymphocytes through an I kappa B kinase-dependent mechanism[J]. Cancer Res,2003,63(3):642-646.
KIMURA YN, WATARI K, FOYOVATI A, et al. Inflammatory stimuli from macrophages and cancer cells synergistically promote tumor growth and angiogenesis[J]. Cancer Sci,2007,98(12):2009-2018.
CARNEIRO-LOBO T C, SCALABRINI L C, MAGALHAES L D S, et al. IKKβ targeting reduces KRAS-induced lung cancer angiogenesis in vitro and in vivo: A potential anti-angiogenic therapeutic target[J]. Lung Cancer,2019,130:169-178.
BELAIBA R S, BONELLO S, ZAHRINGER C, et al. Hypoxia up-regulates hypoxia-inducible factor-1alpha transcription by involving phosphatidylinositol 3-kinase and nuclear factor kappaB in pulmonary artery smooth muscle cells[J]. Mol Biol Cell,2007,18(12):4691-4697.
RIUS J, GUMA M, SCHACHTRUP C, et al. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha[J]. Nature,2008,453(7196):807-811.
CHUNG S E, YEH P Y, LU Y S, et al. Basal levels and patterns of anticancer drug-induced activation of nuclear factor-kappaB (NF-kappaB), and its attenuation by tamoxifen, dexamethasone, and curcumin in carcinoma cells[J]. Biochem Pharmacol,2002,63(9):1709-1716.
JONES D R, BROAD R M, MADRID L V, et al. Inhibition of NF-kappaB sensitizes non-small cell lung cancer cells to chemotherapy-induced apoptosis[J]. Ann Thorac Surg,2000,70(3):930-936.
ZHAO H, WU L, YAN G, et al. Inflammation and tumor progression: Signaling pathways and targeted intervention[J]. Signal Transduct Target Ther,2021,6(1):263.
KONG W, LING X, CHEN Y, et al. Hesperetin reverses P-glycoprotein-mediated cisplatin resistance in DDP-resistant human lung cancer cells via modulation of the nuclear factor-κB signaling pathway[J]. Int J Mol Med,2020,45(4):1213-1224.
GODWIN P, BAIRD A M, HEAVEY S, et al. Targeting nuclear factor-kappa B to overcome resistance to chemotherapy[J]. Front Oncol,2013, doi:10.3389/fonc.2013.00120http://dx.doi.org/10.3389/fonc.2013.00120.
DENLINGER C E, RUNDALL B K, KELLER M D, et al. Proteasome inhibition sensitizes non-small-cell lung cancer to gemcitabine-induced apoptosis[J]. Ann Thorac Surg,2004,78(4):1207-1214.
孙慧茹,杨庆有.温阳散结解毒汤的抗肿瘤作用及其对免疫功能影响的实验研究[J].中医研究,2010,23(4):24-27.
李洪霖,董良,郗昱檀,等.温阳散结汤含药血清通过NF-κB通路调控肿瘤相关巨噬细胞极化对Lewis肺癌的影响[J].现代肿瘤医学,2022,30(18):3257-3264.
张云亭,刘羽茜,蒋宗蓥,等.参苓白术散通过IκBα/NF-κB通路调控Lewis肺癌小鼠肿瘤自噬的研究[J].世界科学技术—中医药现代化,2022,24(4):1487-1494.
于锦超,于敏,莫炜.NF-κB信号通路在肿瘤发生和炎症反应中的作用[J].药物生物技术,2016,23(1):82-85.
VERZELLA D, PESCATORE A, CAPECE D, et al. Life, death, and autophagy in cancer: NF-κB turns up everywhere[J]. Cell Death Dis,2020,11(3):210.
陈雪,何善泉,徐心瑶,等.肺瘤平膏调控肿瘤炎性微环境NF-κB信号通路抑制Lewis肺癌的效应机制[J].北京中医药,2022,41(5):484-489.
阮广欣,周蕾.益气养阴方通过p53依赖AKT/NF-κB信号传导抑制肺癌细胞增殖研究[J].亚太传统医药,2019,15(10):32-36.
程建超,张星星,童佳兵,等.芪玉三龙汤对肺癌小鼠肿瘤组织TLR4/MyD88/NF-κB通路分子表达的影响[J].中药药理与临床,2019,35(5):101-106.
郑阳,宿濛,陈涛,等.加味小陷胸汤基于核转录因子-κB信号通路对非小细胞肺癌荷瘤小鼠的影响实验研究[J].陕西中医,2021,42(1):23-28.
蓝巧玉,蒋锐沅,姚菲,等.基于HMGB1/TLR4/NF-κB通路探究补肺消积饮对气阴两虚型炎症肺癌荷瘤小鼠的肿瘤抑制作用[J].时珍国医国药,2021,32(3):524-528.
陈鉴聪. 健脾化痰方对脾虚痰湿型非小细胞肺癌NF-κB通路调控机制探索[D].广州:广州中医药大学,2019.
张培旭. 基于NF-κB信号通路研究小青龙汤对肺癌H292细胞分泌MUC5AC的调控机制[D].郑州:河南中医药大学,2018.
司海龙,王惠玲,王立芳,等.肺岩宁颗粒对肿瘤相关巨噬细胞及Lewis肺癌细胞侵袭能力的影响[J].河南中医,2018,38(6):853-858.
司海龙,王立芳,邓海滨,等.肺岩宁颗粒调节肿瘤相关巨噬细胞对Lewis肺癌细胞迁移能力影响的研究[J].吉林中医药,2017,37(11):1143-1147.
王惠玲,司海龙,王立芳,等.肺岩宁颗粒对Lewis肺癌小鼠肿瘤生长及肿瘤相关巨噬细胞的影响[J].世界临床药物,2018,39(5):318-323.
谭兆峰. 基于NF-κB相关炎性信号通路探讨芪连扶正胶囊抑制肺癌增殖与转移的机制研究[D].济南:山东中医药大学,2021.
庞兴宇,赵飞,魏学贞,等.青蒿琥酯通过TLR4/NF-κB信号通路对肺癌小鼠移植瘤生长的影响[J].医学动物防制,2022,38(6):527-530,613.
罗雁,王红,阎婷婷,等.蒿甲醚对Lewis肺癌小鼠移植瘤的生长抑制及机制探讨[J].现代预防医学,2017,44(12):2223-2228,2250.
郭旭,杨清竹,杨钰基,等.雷公藤红素对肿瘤的抑制机制[J].高师理科学刊,2022,42(4):60-63.
李涛,严湖,龚长志.雷公藤红素通过NF-κB信号通路抑制非小细胞肺癌A549细胞增殖、侵袭和迁移的机制[J].中国临床研究,2022,35(5):606-612.
朱晓婉,魏静.雷公藤红素升高ROS和抑制NF-κB通路抑制肺癌H460细胞生长[J].中国药师,2020,23(8):1510-1514.
秦慧真,林思,邓玲玉,等.穿心莲内酯药理作用及机制研究进展[J].中国实验方剂学杂志,2022,28(6):272-282.
罗卫民,罗湘玉,刘越峰.穿心莲内酯对肺癌细胞NF-κB的活性以及MMP-9表达的影响[J].中国美容医学,2012,21(14):48-49.
罗湘玉,罗卫民,郑雪松.穿心莲内酯对肺癌细胞MMP-9表达的影响及分子机制研究[J].中国生化药物杂志,2014,34(2):13-16.
张明发,沈雅琴.和厚朴酚及厚朴酚抗肺癌药理作用及机制的研究进展[J].药物评价研究,2022,45(6):1213-1220.
成旭东,陈婷,范玲,等.和厚朴酚通过NF-κB信号通路抑制IL-1诱导的人肺癌细胞H460血管生成[J].中国药理学通报,2022,38(3):380-386.
杨春苗,杨东生,萨仁高娃,等.白藜芦醇化学成分及抗癌药理作用的研究进展[J].广东化工,2022,49(21):108-110.
严静霞,郭勇,张瑞,等.白藜芦醇对肺癌A549细胞增殖及NF-κB表达的影响[J].河北医科大学学报,2016,37(9):1064-1068.
刘玉斌,曹爱国,李之茂,等.白藜芦醇下调NF-κB介导的MMP-9表达抑制人NCI-H446细胞的侵袭迁移[J].实用预防医学,2013,20(9):1141-1144.
史晨旭,杜佳蓉,吴威,等.葛根化学成分及药理作用研究进展[J].中国现代中药,2021,23(12):2177-2195.
李涛,龚长志,朱佳斌,等.葛根素抑制非小细胞肺癌A549细胞增殖、侵袭和迁移的机制探讨[J].现代肿瘤医学,2022,30(1):16-21.
齐娜,段文娟,李雅婧,等.麝香酮药理作用的研究进展[J].世界科学技术—中医药现代化,2020,22(8):3042-3047.
卢鹏,樊晶晶,罗旭,等.麝香酮对肺癌细胞的顺铂耐药和小鼠体内的肿瘤生长的作用[J].广西医科大学学报,2020,37(11):1948-1953.
石玉花,李瑞萍,陈小芸,等.异甘草素抗肿瘤作用及其机制研究进展[J].实用药物与临床,2020,23(4):371-375.
覃月穆,姜泽群,马艳霞,等.异甘草素对人肺癌细胞株H460增殖、凋亡及NF-κB信号通路的影响[J].天然产物研究与开发,2018,30(5):847-855.
李瑞,王宇.黄芪多糖的抗肿瘤作用机制研究进展[J].西部中医药,2022,35(9):150-154.
刘艳玲,袁娟,郭敏,等.基于TLR4/MyD88/NF-κB信号通路探讨黄芪多糖对肺癌小鼠免疫功能的影响及对Th1/Th2的调节作用[J].中国免疫学杂志,2021,37(6):676-682.
徐微,张鑫,潘磊,等.蛇六谷中魔芋葡甘露聚糖对荷Lewis肺癌小鼠脾细胞NF-κB、IκB表达的影响[J].浙江中医杂志,2019,54(4):300-301.
田卉. 茯苓多糖通过TLR4/TRAF6/NF-κB信号传导通路发挥免疫调节作用机制的研究[D].重庆:重庆医科大学,2019.
周玉,汪萍,杨建课.黄精多糖抗肿瘤作用的研究进展[J].湖北中医杂志,2022,44(7):63-66.
龙婷婷. 基于TLR4-MAPK/NF-κB信号通路探讨黄精多糖免疫调节抗肿瘤作用机制研究[D].重庆:重庆医科大学,2018.
周志勇,陈亚昕,李德鸿,等.竹节参总皂苷通过抑制NF-κB介导的炎性反应改善小鼠肿瘤恶病质研究[J].中国药理学通报,2018,34(4):532-537.
高贵洲,张宏瑞,梁晓华,等.竹节参皂苷通过Toll样受体4/核转录因子-κB信号通路调控免疫功能对肺癌大鼠模型的影响[J].陕西医学杂志,2020,49(12):1539-1542,1548.
罗宗源,任丹,刘思言,等.蛇床子素衍生物的结构、合成与生物活性研究进展[J].中国药物化学杂志,2022,32(4):314-322.
彭建明,朱扣柱,叶记林,等.蛇床子素对肺癌H1299细胞增殖和凋亡的作用[J].天津医药,2020,48(2):87-90.
0
Views
29
下载量
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution