Research Progress of Anti-lung Cancer Effect of Quercetin <i>in Vitro</i>

HU Fenqing; LI Cuibai; DANG Lingjing; ZOU Cheng; ZHAO Qing; SHAO Yuefeng

doi:10.13386/j.issn1002-0306.2021080017

Volume 43 Issue 18

Sep. 2022

Turn off MathJax

Article Contents

Abstract

References

Science and Technology of Food Industry > 2022 > 43(18): 416-424. > DOI: 10.13386/j.issn1002-0306.2021080017

HU Fenqing, LI Cuibai, DANG Lingjing, et al. Research Progress of Anti-lung Cancer Effect of Quercetin in Vitro[J]. Science and Technology of Food Industry, 2022, 43(18): 416−424. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2021080017.

Citation:

PDF (2376 KB)

Research Progress of Anti-lung Cancer Effect of Quercetin in Vitro

1.
Dehong Vocational College, Mangshi 678400, China
2.
College of Pharmacy, Kunming Medical University, Kunming 650599, China
3.
College of Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming 650599, China

More Information

Received Date: August 03, 2021
Available Online: July 03, 2022

Graphical Abstract

Abstract

Abstract

Quercetin is a flavonol compound containing o-diphenol hydroxyl and resorcinol hydroxyl. In order to analyze the current status of quercetin in vitro anti-lung cancer, this article uses domestic Knowledge Network, Wanfang, foreign SpringerLink and PubMed databases, entered the subject terms “quercetin”, “quercetin derivative”, “lung cancer”, and then searched for quercetin’s anti-lung cancer in recent years. Retrieving the relevant data on the research of quercetin and its derivatives in anti-lung cancer in recent years, review of its new preparations, derivatives and mechanism of action. The new anti-lung cancer preparations of quercetin include nanoparticles, nanoemulsions, nanomicelles, liposomes and other preparations. From more than 120 quercetin derivatives that have been synthesized, 11 compounds with stronger effects on lung cancer than quercetin are found. Quercetin and its derivative play an anti-lung cancer effect by inducing cell apoptosis, inhibiting enzyme activity, blocking cell cycle, and reversing tumor drug resistance. It could provide a basis for the research, development and utilization of quercetin and its derivatives in lung cancer.
- quercetin,
- anti-lung cancer in vitro,
- quercetin derivatives,
- mechanism

FullText(HTML)

References (62)

References

[1]	SONG X Y, HU Z, TIAN Y F, et al. Does irradiation for initial primary lung cancer affect the risk of metachronous second primary lung cancer?[J]. Radiation and Environmental Biophysics,2021,60(3):475−483. doi: 10.1007/s00411-021-00923-9
[2]	ZHANG N, WANG Y J, YU H J, et al. Distance to highway and factory density related to lung cancer death and associated spatial heterogeneity in effects in Jiading District, Shanghai[J]. Environmental Science and Pollution Research International,2021:64536−64551.
[3]	ABHARZANJANI F, HEMMATI M. Protective effects of quercetin and resveratrol on aging markers in kidney under high glucose condition: In vivo and in vitro analysis[J]. Molecular Biology Reports,2021,48(7):5435−5442. doi: 10.1007/s11033-021-06550-3
[4]	DHANYA R, KARTHA C C. Quercetin improves oxidative stress-induced pancreatic beta cell alterations via mTOR-signaling[J]. Molecular and Cellular Biochemistry,2021,476(11):3879−3887. doi: 10.1007/s11010-021-04193-3
[5]	MALEKI D P, SADOUGHI F, ASEMI Z, et al. Anti-cancer properties of quercetin in osteosarcoma[J]. Cancer Cell International,2021,21(1):349. doi: 10.1186/s12935-021-02067-8
[6]	ERDOGAR N, AKKIN S, VARAN G, et al. Erlotinib complexation with randomly methylated β-cyclodextrin improves drug solubility, intestinal permeability, and therapeutic efficacy in non-small cell lung cancer[J]. Pharmaceutical Development and Technology,2021,26(7):797−806. doi: 10.1080/10837450.2021.1946695
[7]	LIAN Z Y, PANG J J, GUO Y X, et al. Study on the synthesis and antitumor activity of quercetin-3-O-acyl ester[J]. Biochemical,2021,7(3):40−43.
[8]	LÜ F N, HUANG J, CHENG J Q, et al. Preparation and cytological study of quercetin-loaded PNIPAm nanogel[J]. Journal of Nanjing University of Traditional Chinese Medicine,2020,36(2):197−204.
[9]	曹彦平. 不同粒径槲皮素纳米混悬剂的抗肿瘤活性研究[D]. 开封: 河南大学, 2019 CAO Y P. Study on the anti-tumor activity of quercetin nanosuspensions with different particle sizes [D]. Kaifeng: Henan University, 2019.
[10]	魏志豪. 羟基喜树碱与槲皮素联合用药纳米混悬剂的体内外抗肿瘤活性研究[D]. 开封: 河南大学, 2019 WEI Z H. Study on the anti-tumor activity of hydroxycamptothecin and quercetin combined drug nanosuspension in vivo and in vitro [D]. Kaifeng: Henan University, 2019.
[11]	徐浩, 高艺璇, 王向涛. 槲皮素纳米混悬剂的制备、表征及抗乳腺癌研究[J]. 中草药,2019,50(1):42−51. [XU H, GAO Y X, WANG X T. Preparation, characterization and anti-breast cancer research of quercetin nanosuspension[J]. Chinese Herbal Medicine,2019,50(1):42−51. doi: 10.7501/j.issn.0253-2670.2019.01.009 XU H, GAO Y X, WANG X T. Preparation, characterization and anti-breast cancer research of quercetin nanosuspension [J]. Chinese herbal medicine, 2019, 50(1): 42-51. doi: 10.7501/j.issn.0253-2670.2019.01.009
[12]	胡凯莉. 槲皮素调节肿瘤微环境提高纳米粒的瘤内渗透、滞留及抗肿瘤效果[C]//2018年第十二届中国药物制剂大会论文集[出版者不详]. 2018: 297−298. HU K L. Quercetin regulates the tumor microenvironment and improves the intratumoral penetration, retention and anti-tumor effects of nanoparticles [C]//Proceedings of the 12th China Pharmaceutical Preparations Conference in 2018 [Publisher unknown]. 2018: 297−298.
[13]	杜倩, 汤洋, 陈剑秋, 等. 槲皮素和白藜芦醇共载磁性固体脂质纳米粒的制备及其抑瘤作用评价[J]. 中国实验方剂学杂志,2019,25(10):109−114. [DU Q, TAGN Y, CHENG J Q, et al. Preparation of quercetin and resveratrol co-loaded magnetic solid lipid nanoparticles and evaluation of their anti-tumor effect[J]. Chinese Journal of Experimental Formulas,2019,25(10):109−114. doi: 10.13422/j.cnki.syfjx.20190209 DU Q, TAGN Y, CHENG J Q, et al. Preparation of quercetin and resveratrol co-loaded magnetic solid lipid nanoparticles and evaluation of their anti-tumor effect [J]. Chinese Journal of Experimental Formulas, 2019, 25(10): 109-114. doi: 10.13422/j.cnki.syfjx.20190209
[14]	WANG T. Construction of ginkgo nanostarch/quercetin drug loading system and its anti-tumor activity [D]. Nanjing: Nanjing Forestry University, 2020.
[15]	刘康. 槲皮素和紫杉醇共输送肺吸入油酰壳聚糖纳米聚合微球的构建及药动学研究[D]. 潍坊: 潍坊医学院, 2017 LIU K. Construction and pharmacokinetics of oleoyl chitosan nano-polymerized microspheres for co-delivery of quercetin and paclitaxel[D]. Weifang: Weifang Medical College, 2017.
[16]	WANG Y, YU H, WANG S, et al. Targeted delivery of quercetin by nanoparticles based on chitosan sensitizing paclitaxel-resistant lung cancer cells to paclitaxel[J]. Materials Science & Engineering C,2021,119:111442.
[17]	ARBAIN N H, SALIM N, MASOUMI H R F, et al. In vitro evaluation of the inhalable quercetin loaded nanoemulsion for pulmonary delivery[J]. Drug Delivery and Translational Research,2019,9(2):497−507. doi: 10.1007/s13346-018-0509-5
[18]	ARBAIN N H, BASRI M, SALIM N, et al. Development and characterization of aerosol nanoemulsion system encapsulating low water soluble quercetin for lung cancer treatment[J]. Materials Today: Proceedings,2018:5.
[19]	袁志平. 脂质体槲皮素的抗肿瘤实验研究[D]. 成都: 四川大学, 2006 YUAN Z P. Experimental study on anti-tumor effect of liposomal quercetin [D]. Chengdu: Sichuan University, 2006.
[20]	RIAZ M K, ZHANG X, WONG K H, et al. Pulmonary delivery of transferrin receptors targeting peptide surface-functionalized liposomes augments the chemotherapeutic effect of quercetin in lung cancer therapy[J]. International Journal of Nanomedicine,2019,14:2879−2902. doi: 10.2147/IJN.S192219
[21]	ZHOU X, LIU H Y, ZHAO H, et al. RGD-modified nanoliposomes containing quercetin for lung cancer targeted treatment[J]. Onco Targets and Therapy,2018,11:5397−5405. doi: 10.2147/OTT.S169555
[22]	LI C, GAO L F, ZHANG Y, et al. Preparation of quercetin loaded microparticles and their antitumor activity against human lung cancer cells (A549) in vitro[J]. Current Pharmaceutical Biotechnology,2019,20(11):945−954. doi: 10.2174/1573407215666190628145902
[23]	WANG B J, ZHANG W, ZHOU X D, et al. Development of dual-targeted nano-dandelion based on an oligomeric hyaluronic acid polymer targeting tumor-associated macrophages for combination therapy of non-small cell lung cancer[J]. Drug Delivery,2019,26(1):1265−1279. doi: 10.1080/10717544.2019.1693707
[24]	XU Z L, HU L L, MING J J, et al. Self-gated porous organic polymer as drug delivery system for pH stimuli-responsive controlled quercetin release[J]. Microporous and Mesoporous Materials,2020:303.
[25]	LAKSHMI B A, BAE J Y, AN J H, et al. Facile design and spectroscopic characterization of novel bio-inspired quercetin-conjugated tetrakis (dimethylsulfoxide) dichlororuthenium(II) complex for enhanced anticancer properties[J]. Inorganica Chimica Acta,2019:495.
[26]	LAKSHMI B A, BAE J Y, AN J H, et al. Nanoclusters prepared from ruthenium (II) and quercetin for fluorometric detection of cobalt (II), and a method for screening their anticancer drug activity[J]. Microchimica Acta,2019,186(8):539. doi: 10.1007/s00604-019-3657-5
[27]	LAKSHMI B A, KIM S. Quercetin mediated gold nanoclusters explored as a dual functional nanomaterial in anticancer and bio-imaging disciplines[J]. Colloids and Surfaces B: Biointerfaces,2019, 178:230−237.
[28]	郭中原, 贾景景, 梁曜华, 等. 烯丙基槲皮素衍生物的合成及活性评价[J]. 中国药学杂志,2016,51(6):442−448. [GUO Z Y, JIA J J, LIANG Y H, et al. Synthesis and activity evaluation of allyl quercetin derivatives[J]. Chinese Pharmaceutical Journal,2016,51(6):442−448. GUO Z Y, JIA J J, LIANG Y H, et al. Synthesis and activity evaluation of allyl quercetin derivatives [J]. Chinese Pharmaceutical Journal, 2016, 51(6): 442-448.
[29]	冯亚莉, 卢令攀, 翟广玉. 槲皮素衍生物抗肿瘤活性研究进展[J]. 中国中药杂志,2020,45(15):3565−3574. [FANG Y L, LU L P, ZHAI G Y. Research progress of anti-tumor activity of quercetin derivatives[J]. Chinese Journal of Traditional Chinese Medicine,2020,45(15):3565−3574. FANG Y L, LU L P, ZHAI G Y. Research progress of anti-tumor activity of quercetin derivatives [J]. Chinese Journal of Traditional Chinese Medicine, 2020, 45(15): 3565-3574.
[30]	贾景景, 郭中原, 梁曜华, 等. 槲皮素衍生物的合成及其抗肿瘤活性研究[J]. 中国药学杂志,2016,51(23):2013−2017. [JIA J J, GUO Z Y, LIANG Y H, et al. Synthesis of quercetin derivatives and their anti-tumor activity[J]. Chinese Pharmaceutical Journal,2016,51(23):2013−2017. JIA J J, GUO Z Y, LIANG Y H, et al. Synthesis of quercetin derivatives and their anti-tumor activity [J]. Chinese Pharmaceutical Journal, 2016, 51(23): 2013-2017.
[31]	渠文涛, 朱玮, 翟广玉, 等. 槲皮素衍生物的合成及生物活性研究进展[J]. 化学研究,2012,23(4):101−110. [QI W T, ZHU W, QI G Y, et al. Research progress on synthesis and biological activity of quercetin derivatives[J]. Chemical Research,2012,23(4):101−110. doi: 10.3969/j.issn.1008-1011.2012.04.025 QI W T, ZHU W, QI G Y, et al. Research progress on synthesis and biological activity of quercetin derivatives [J]. Chemical Research, 2012, 23(4): 101-110. doi: 10.3969/j.issn.1008-1011.2012.04.025
[32]	王恩霞. 7-O-香叶基槲皮素体外诱导肺癌细胞发生凋亡与自噬作用的研究[D]. 大连: 大连医科大学, 2016 WANG E X. 7-O-geranyl quercetin induces lung cancer cell apoptosis and autophagy in vitro [D]. Dalian: Dalian Medical University, 2016.
[33]	ESCOBR Z, SOLANO C, LARSSON R, et al. Synthesis of poinsettifolin A[J]. Tetrahedron,2014,70:9052−9056. doi: 10.1016/j.tet.2014.10.021
[34]	陈积常, 黄初升, 刘红星, 等. 具有生物活性的异物烯基及香叶基黄酮类化合物[J]. 化工技术与开发,2013,42(1):12−17. [CHENG J C, HUAGN C S, LIU H X, et al. Biologically active foreign body alkenyl and geranyl flavonoids[J]. Chemical Technology and Development,2013,42(1):12−17. doi: 10.3969/j.issn.1671-9905.2013.01.004 CHENG J C, HUAGN C S, LIU H X, et al. Biologically active foreign body alkenyl and geranyl flavonoids [J]. Chemical Technology and Development, 2013, 42(1): 12-17. doi: 10.3969/j.issn.1671-9905.2013.01.004
[35]	ALPER P, ERKISA M, MUTLU G H, et al. Synthesis, characterization, anticancer and antioxidant activity of new nickel(II) and copper(II) flavonoid complexes[J]. Journal of Molecular Structure,2020,25(1):161−177.
[36]	刘伟. 奥希替尼联合槲皮素对非小细胞肺癌H1975细胞增殖的协同抑制作用[D]. 合肥: 安徽医科大学, 2019 LIU W. Synergistic inhibitory effect of osimertinib combined with quercetin on the proliferation of non-small cell lung cancer H1975 cells [D]. Hefei: Anhui Medical University, 2019.
[37]	苏珊, 邹建军, 孔少颜, 等. 槲皮素对小细胞肺癌细胞株H446的凋亡调控作用[J]. 临床肺科杂志,2015,20(6):987−989. [SU S, ZOU J J, KONG S Y, et al. The regulatory effect of quercetin on the apoptosis of small cell lung cancer cell line H446[J]. Journal of Clinical Pulmonology,2015,20(6):987−989. doi: 10.3969/j.issn.1009-6663.2015.06.006 SU S, ZOU J J, KONG S Y, et al. The regulatory effect of quercetin on the apoptosis of small cell lung cancer cell line H446 [J]. Journal of Clinical Pulmonology, 2015, 20(6): 987-989. doi: 10.3969/j.issn.1009-6663.2015.06.006
[38]	袁玫, 王松, 张増雷, 等. 槲皮素通过抑制核因子-κB表达诱导A549细胞凋亡[J]. 中国老年学杂志,2015,35(7):1921−1923. [YUAN M, WANG S, ZHANG Z L, et al. Quercetin induces A549 cell apoptosis by inhibiting the expression of nuclear factor-κB[J]. Chinese Journal of Gerontology,2015,35(7):1921−1923. doi: 10.3969/j.issn.1005-9202.2015.07.085 YUAN M, WANG S, ZHANG Z L, et al. Quercetin induces A549 cell apoptosis by inhibiting the expression of nuclear factor-κB [J]. Chinese Journal of Gerontology, 2015, 35(7): 1921-1923. doi: 10.3969/j.issn.1005-9202.2015.07.085
[39]	刘涛, 张雅雅, 许英艺, 等. 槲皮素对人小细胞肺癌H446细胞增殖和凋亡的影响[J]. 中国肿瘤生物治疗杂志,2014,21(2):169−174. [LIU T, ZHANG Y Y, XU Y Y, et al. Effects of quercetin on proliferation and apoptosis of human small cell lung cancer H446 cells[J]. Chinese Journal of Cancer Biotherapy,2014,21(2):169−174. doi: 10.3872/j.issn.1007-385X.2014.02.010 LIU T, ZHANG Y Y, XU Y Y, et al. Effects of quercetin on proliferation and apoptosis of human small cell lung cancer H446 cells [J]. Chinese Journal of Cancer Biotherapy, 2014, 21(2): 169-174. doi: 10.3872/j.issn.1007-385X.2014.02.010
[40]	WANG Q, CHEN A K, LU H J, et al. Quercetin radiosensitizes non-small cell lung cancer cells through the regulation of miR-16-5p/WEE1 axis[J]. IUBMB Life,2020,72(5):1012−1022. doi: 10.1002/iub.2242
[41]	CHUANG C H, CHAN S T, CHEN C H, et al. Quercetin enhances the antitumor activity of trichostatin A through up-regulation of p300 protein expression in p53 null cancer cells[J]. Chemico-Biological Interactions,2019,306:54−61. doi: 10.1016/j.cbi.2019.04.006
[42]	徐晓, 刘进, 张珂. 槲皮素对人肺癌细胞株A-549细胞增殖的抑制作用[J]. 浙江医学,2014,36(7):557−560,581,635. [XU X, LIU J, ZHANG K. Inhibitory effect of quercetin on the proliferation of human lung cancer cell line A-549[J]. Zhejiang Medicine,2014,36(7):557−560,581,635. XU X, LIU J, ZHANG K. Inhibitory effect of quercetin on the proliferation of human lung cancer cell line A-549 [J]. Zhejiang Medicine, 2014, 36(7): 557-560, 581, 635.
[43]	张隽, 曹培国, 潘宇亮. 槲皮素联合白藜芦醇对小鼠Lewis肺癌细胞生长的抑制作用[J]. 肿瘤防治研究,2012,39(8):936−939. [ZHANG X, CAO G P, PAN Y L. Inhibitory effect of quercetin combined with resveratrol on the growth of mouse Lewis lung cancer cells[J]. Cancer Research,2012,39(8):936−939. ZHANG X, CAO G P, PAN Y L. Inhibitory effect of quercetin combined with resveratrol on the growth of mouse Lewis lung cancer cells [J]. Cancer Research, 2012, 39(8): 936-939.
[44]	王玉波, 卢兆桐, 张庆广, 等. 槲皮素对肺腺癌细胞A549/DDP多药耐药的逆转作用[J]. 滨州医学院学报,2013,36(2):86−89. [WANG Y B, LU Z T, ZHANG Q G, et al. The reversal effect of quercetin on multidrug resistance of lung adenocarcinoma cell line A549/DDP[J]. Journal of Binzhou Medical University,2013,36(2):86−89. doi: 10.3969/j.issn.1001-9510.2013.02.002 WANG Y B, LU Z T, ZHANG Q G, et al. The reversal effect of quercetin on multidrug resistance of lung adenocarcinoma cell line A549/DDP [J]. Journal of Binzhou Medical University, 2013, 36(2): 86-89. doi: 10.3969/j.issn.1001-9510.2013.02.002
[45]	赵存玲, 郭风龙, 谈燕燕, 等. 槲皮素通过EMT途径抑制H3122细胞迁移[J]. 河北医药,2019,41(2):170−173. [ZHAO C L, GUO F L, TAN Y Y, et al. Quercetin inhibits the migration of H3122 cells through the EMT pathway[J]. Hebei Medicine,2019,41(2):170−173. doi: 10.3969/j.issn.1002-7386.2019.02.002 ZHAO C L, GUO F L, TAN Y Y, et al. Quercetin inhibits the migration of H3122 cells through the EMT pathway [J]. Hebei Medicine, 2019, 41(2): 170-173. doi: 10.3969/j.issn.1002-7386.2019.02.002
[46]	姜益, 庞军, 吴晓东, 等. 槲皮素对TGF-β诱导的人肺癌A549细胞上皮间质转化的影响[J]. 中国现代医生,2013,51(5):6−8,11. [JIANG Y, PENG J, WU X D, et al. The effect of quercetin on the epithelial-mesenchymal transition of human lung cancer A549 cells induced by TGF-β[J]. Modern Chinese Doctor,2013,51(5):6−8,11. JIANG Y, PENG J, WU X D, et al. The effect of quercetin on the epithelial-mesenchymal transition of human lung cancer A549 cells induced by TGF-β[J]. Modern Chinese Doctor, 2013, 51(5): 6-8, 11.
[47]	LI H, TAN L, ZHANG J W, et al. Quercetin is the active component of Yang-Yin-Qing-Fei-Tang to induce apoptosis in non-small cell lung cancer[J]. The American Journal of Chinese Medicine,2019,47(4):879−893. doi: 10.1142/S0192415X19500460
[48]	王静, 袁媛, 彭佳, 等. 槲皮素通过Stat3/Mcl-1途径介导肺癌PC9/GR细胞凋亡的研究[J]. 安徽医科大学学报,2017,52(12):1782−1785. [WANG J, YUAN Y, PANG J, et al. Quercetin mediates lung cancer PC9/GR cell apoptosis through Stat3/Mcl-1 pathway[J]. Journal of Anhui Medical University,2017,52(12):1782−1785. WANG J, YUAN Y, PANG J, et al. Quercetin mediates lung cancer PC9/GR cell apoptosis through Stat3/Mcl-1 pathway [J]. Journal of Anhui Medical University, 2017, 52(12): 1782-1785.
[49]	ZHUANG Z J. A comprehensive network pharmacology-based strategy to investigate multiple mechanisms of HeChan tablet on lung cancer[J]. Evidence-Based Complementary and Alternative Medicine,2020:7658342.
[50]	DONG Y, YANG J, YANG L Y, et al. Quercetin inhibits the proliferation and metastasis of human non-small cell lung cancer cell line: The key role of Src-mediated fibroblast growth factor-inducible 14 (Fn14)/ nuclear factor kappa B (NF-κB) pathway[J]. Medical Science Monitor,2020,26:e920537.
[51]	文兰香, 覃世运, 陈丽君. 槲皮素调控AMPK/mTOR通路对肺癌A549细胞自噬的影响[J]. 中国免疫学杂志,2020,36(19):2375−2379. [WENG L X, TAN S Y, CHENG L J. Quercetin regulates AMPK/mTOR pathway on autophagy in lung cancer A549 cells[J]. Chinese Journal of Immunology,2020,36(19):2375−2379. doi: 10.3969/j.issn.1000-484X.2020.19.019 WENG L X, TAN S Y, CHENG L J. Quercetin regulates AMPK/mTOR pathway on autophagy in lung cancer A549 cells [J]. Chinese Journal of Immunology, 2020, 36(19): 2375-2379. doi: 10.3969/j.issn.1000-484X.2020.19.019
[52]	李华洋, 许婧, 那辉, 等. 槲皮素通过STAT3信号通路抑制肺癌A549细胞迁移和侵袭[J]. 国际药学研究杂志,2017,44(3):262−266. [LI H Y, XU J, NA H, et al. Quercetin inhibits the migration and invasion of lung cancer A549 cells through the STAT3 signaling pathway[J]. International Journal of Pharmaceutical Research,2017,44(3):262−266. LI H Y, XU J, NA H, et al. Quercetin inhibits the migration and invasion of lung cancer A549 cells through the STAT3 signaling pathway [J]. International Journal of Pharmaceutical Research, 2017, 44(3): 262-266.
[53]	黄震洲, 陈美娟, 熊飞, 等. 周氏克金岩方有效成分槲皮素促进肺癌细胞NCI-H460凋亡的相关机制研究[J]. 南京中医药大学学报,2012,28(3):235−237. [HUANG Z Z, CHENG M J, XIONG F, et al. Study on the related mechanism of quercetin, an effective component of Zhou's Kejinyan prescription, promoting apoptosis of lung cancer cell NCI-H460[J]. Journal of Nanjing University of Traditional Chinese Medicine,2012,28(3):235−237. doi: 10.3969/j.issn.1000-5005.2012.03.012 HUANG Z Z, CHENG M J, XIONG F, et al. Study on the related mechanism of quercetin, an effective component of Zhou's Kejinyan prescription, promoting apoptosis of lung cancer cell NCI-H460 [J]. Journal of Nanjing University of Traditional Chinese Medicine, 2012, 28(3): 235-237. doi: 10.3969/j.issn.1000-5005.2012.03.012
[54]	HUANG Z Z. Study on molecular mechanism of cytotoxic ingredients in Zhou's Kejinyan recipe in treating lung cancer [D]. Nanjing: Nanjing University of Chinese Medicine, 2012.
[55]	WU T C, CHAN S T, CHANG C N, et al. Quercetin and chrysin inhibit nickel-induced invasion and migration by downregulation of TLR4/NF-κB signaling in A549 cells[J]. Chemico-Biological Interactions,2018,292:101−109. doi: 10.1016/j.cbi.2018.07.010
[56]	LIU D L, WU K, JIE H Z, et al. The expression and significance of cyclooxygenase-2, matrix metalloproteinase 2, and matrix metalloproteinase 9 in non-small cell lung cancer[J]. Cancer Progress,2020,18(12):1236−1239.
[57]	CAO J, XU J Q, LUO X J, et al. Changes in serum levels of matrix metalloproteinases, squamous cell carcinoma antigens, keratin 19 fragments, carcinoembryonic antigens, neuron enolase levels in peripheral lung cancer and their clinical significance[J]. China Primary Medicine,2021,28(6):844−848.
[58]	KONG H X, LI H J, XU J, et al. Changes of serum MMP-9, HE4, CYFRA21-1, CEA, NSE levels in patients with lung cancer and their clinical significance[J]. Shandong Medicine,2017,57(32):73−75.
[59]	赵欣, 张健. 槲皮素抑制肺癌肿瘤细胞的生长和转移的机制[J]. 中南大学学报(医学版),2015,40(6):592−597. [ZHAO X, ZHANG J. The mechanism of quercetin inhibiting the growth and metastasis of lung cancer cells[J]. Journal of Central South University (Medical Edition),2015,40(6):592−597. doi: 10.11817/j.issn.1672-7347.2015.06.004 ZHAO X, ZHANG J. The mechanism of quercetin inhibiting the growth and metastasis of lung cancer cells [J]. Journal of Central South University (Medical Edition), 2015, 40(6): 592-597. doi: 10.11817/j.issn.1672-7347.2015.06.004
[60]	ALBRECHT C, CITTADINI C M, SORIA A E. Pharmacological activity of quercetin and 5 caffeoylquinic acid oral intake in male balb/c mice with lung adenocarcinoma[J]. Archives of Medical Research,2020,51(1):8−12. doi: 10.1016/j.arcmed.2019.11.006
[61]	ZHAN X J, ZHANG R X, YANG S H, et al. Experimental study on the sensitization effect of quercetin on the chemotherapeutic drugs of human lung cancer cell line A549 (in English)[J]. Chinese-German Journal of Clinical Oncology,2012,11(7):380−383. doi: 10.1007/s10330-012-0998-5
[62]	WANG Y H, YU H L, WANG S S, et al. Targeted delivery of quercetin by nanoparticles based on chitosan sensitizing paclitaxel-resistant lung cancer cells to paclitaxel[J]. Materials Science & Engineering. C, Materials for Biological Applications,2021,119:111442.