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上海中医药大学 中药学院,上海 201203
Received:28 April 2019,
Published Online:01 August 2019,
Published:20 February 2020
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Fei YAN, Ying LIU, Nian-ping FENG. Research Progress of Nano-drug Delivery Systems for Active Ingredients from Chinese Materia Medica by Modulating EMT to Inhibit Tumor Metastasis[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(4): 235-241.
Fei YAN, Ying LIU, Nian-ping FENG. Research Progress of Nano-drug Delivery Systems for Active Ingredients from Chinese Materia Medica by Modulating EMT to Inhibit Tumor Metastasis[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(4): 235-241. DOI: 10.13422/j.cnki.syfjx.20192246.
上皮间质转化(EMT)是在Twist,Snail及Zeb等家族转录因子作用下,上皮细胞失去极性,获得迁移间质特性的过程。EMT在肿瘤发生、发展和转移等多阶段发挥着重要作用。某些中药有效成分可通过多靶点激活转录因子以及相关信号通路来抑制EMT,但在溶解性、稳定性、组织特异性和安全性等方面存在不足,从而限制其药效发挥。纳米递送系统可以增强中药有效成分抑制EMT介导的肿瘤转移效果,降低药物毒副作用,提高其成药性。该文对调控EMT的中药有效成分纳米递送系统及其在抑制肿瘤转移方面的研究进展进行了综述,为相关药物的研发提供了参考依据。
The epithelial-to-mesenchymal transition (EMT)
a process during which cells undergo transition from a polarized epithelial phenotype to a non-polarized mesenchymal phenotype
executed by transcription factors of Twist
Snail and Zeb families. EMT plays an important role in multiple stages of cancer progression such as initiation
tumor growth
and metastasis. Some active ingredients from Chinese materia medica can inhibit EMT by regulating transcription factors and signaling pathways by multiple targets. However
their therapeutic effect was hindered due to various limitation such as solubility
stability
tissue specificity and safety. Therefore
in order to improve the druggability of active ingredients from Chinese materia medica
enhance the therapeutic effect in inhibiting tumor metastasis mediated by EMT and reduce the toxic and side effects
a variety of nano-drug delivery systems have been developed in recent years. Here
we made a review about these drug delivery systems modulating EMT and their research progress in inhibiting tumor metastasis.
A W Lambert , D R Pattabiraman , R A Weinberg . Emerging biological principles of metastasis [J]. Cell , 2017 , 168 ( 4 ): 670 - 691 .
B Salehi , E M Varoni , M Sharifi-Rad , et al . Epithelial-mesenchymal transition as a target for botanicals in cancer metastasis [J]. Phytomedicine , 2019 , 55 : 125 - 136 .
X H LIANG . EMT:new signals from the invasive front [J]. Oral Oncol , 2011 , 47 ( 8 ): 686 - 687 .
T Brabletz , R Kalluri , M A Nieto , et al . EMT in cancer [J]. Nat Rev Cancer , 2018 , 18 ( 2 ): 128 - 134 .
张青云 , 傅俊江 , 陈汉春 . 上皮间质转化介导肿瘤转移的分子机制 [J]. 生命科学研究 , 2018 , 22 ( 6 ): 503 - 510 .
李优 , 王剑 , 牟好 , 等 . 姜黄素通过PI3K/AKT/mTOR通路抑制TGF- β 1 诱导的肺癌细胞上皮间质转化 [J]. 肿瘤学杂志 , 2016 , 22 ( 8 ): 607 - 614 .
L CAO , X XIAO , J J LEI , et al . Curcumin inhibits hypoxia-induced epithelial-mesenchymal transition in pancreatic cancer cells via suppression of the hedgehog signaling pathway [J]. Oncol Rep , 2016 , 35 ( 6 ): 3728 - 3734 .
朱耀东 , 刘延庆 . 中药抑制肿瘤上皮间质转化的研究 [J]. 中国实验方剂学杂志 , 2014 , 20 ( 6 ): 228 - 232 .
M M Baruah , A P Khandwekar , N Sharma . Quercetin modulates Wnt signaling components in prostate cancer cell line by inhibiting cell viability,migration,and metastases [J]. Tumour Biol , 2016 , 37 ( 10 ): 14025 - 14034 .
高彩芳 . 纳米技术在改善中药有效成分成药性中的应用 [J]. 中草药 , 2018 , 49 ( 12 ): 2754 - 2762 .
吴芸 , 严国俊 , 蔡宝昌 . 纳米技术在中药领域的研究进展 [J]. 中草药 , 2011 , 42 ( 2 ): 403 - 408 .
D Pradella , C Naro , C Sette , et al . EMT and stemness:flexible processes tuned by alternative splicing in development and cancer progression [J]. Mol Cancer , 2017 , 16 ( 1 ): 8 .
J P Thiery , H Acloque , R Y J HUANG , set al . Epithelial-mesenchymal transition in development and diseases [J]. Cell , 2009 , 139 ( 5 ): 871 - 890 .
S Lamouille , J XU , R Derynck . Molecular mechanisms of epithelial-mesenchymal transition [J]. Nat Rev Mol Cell Biol , 2014 , 15 ( 3 ): 178 - 196 .
R Heery , S P Finn , S Cuffe , et al . Long non-coding RNAs:key regulators of epithelial-mesenchymal transition,tumour drug resistance and cancer stem cells [J]. Cancers(Basel) , 2017 , 9 ( 4 ): E38 .
R Kalluri , R A Weinberg . The basics of epithelial-mesenchymal transition [J]. J Clin Invest , 2009 , 119 ( 6 ): 1420 - 1428 .
X LIU , F YUN , L SHI , et al . Roles of signaling pathways in the epithelial-mesenchymal transition in cancer [J]. Asian Pac J Cancer Prev , 2015 , 16 ( 15 ): 6201 - 6206 .
M Diepenbruck , G Christofori . Epithelial-mesenchymal transition (EMT) and metastasis:yes,no,maybe? [J]. Curr Opin Cell Biol , 2016 , 43 : 7 - 13 .
S Kaufhold , B Bonavida . Central role of Snail1 in the regulation of EMT and resistance in cancer:a target for therapeutic intervention [J]. J Exp Clin Cancer Res , 2014 , 33 : 62 .
F LIU , L N GU , B E SHAN , et al . Biomarkers for EMT and MET in breast cancer:an update [J]. Oncol Lett , 2016 , 12 ( 6 ): 4869 - 4876 .
A Barrallo-Gimeno , M A Nieto . The Snail genes as inducers of cell movement and survival:implications in development and cancer [J]. Development , 2005 , 132 ( 14 ): 3151 - 3161 .
H W YANG , S A Lee , J M Shin , et al . Glucocorticoids ameliorate TGF- β 1 -mediated epithelial-to-mesenchymal transition of airway epithelium through MAPK and Snail/Slug signaling pathways [J]. Sci Rep , 2017 , 7 ( 1 ): 3486 .
M H YANG , S S Hsu , H W WANG , et al . Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition [J]. Nat Cell Biol , 2010 , 12 ( 10 ): 982 - 992 .
Y Kawarada , Y Inoue , F Kawasaki , et al . TGF- β induces p53/Smads complex formation in thePAI-1promoter to activate transcription [J]. Sci Rep , 2016 , 6 : 35483 .
F Y XU , C W LIU , D D ZHOU , et al . TGF/SMAD pathways and its regulation in hepatic fibrosis [J]. J Histochem Cytochem , 2016 , 64 ( 3 ): 157 - 167 .
D WANG , P LU , H ZHANG , et al . Oct-4 and Nanog promote the epithelial-mesenchymal transition of breast cancer stem cells and are associated with poor prognosis in breast cancer patients [J]. Oncotarget , 2014 , 5 ( 21 ): 10803 - 10815 .
P J Miettinen , R Ebner , A R Lopez , et al . TGF-beta induced transdifferentiation of mammary epithelial cells to mesenchymal cells:involvement of type I receptors [J]. J Cell Biol , 1994 , 127 ( 6Pt2 ): 2021 - 2036 .
C Y Park , K N Min , J Y Son , et al . An novel inhibitor of TGF- β type I receptor,IN-1130,blocks breast cancer lung metastasis through inhibition of epithelial-mesenchymal transition [J]. Cancer Lett , 2014 , 351 ( 1 ): 72 - 80 .
朱宏明 . Notch信号通路介导EMT与肿瘤侵袭转移的研究进展 [J]. 肿瘤学杂志 , 2018 , 24 ( 8 ): 808 - 812 .
T Valenta , G Hausmann , K Basler . The many faces and functions of β -catenin [J]. EMBO J , 2012 , 31 ( 12 ): 2714 - 2736 .
M Anson , A M Crain-Denoyelle , V Baud , et al . Oncogenic β -catenin triggers an inflammatory response that determines the aggressiveness of hepatocellular carcinoma in mice [J]. J Clin Invest , 2012 , 122 ( 2 ): 586 - 599 .
J C CAI , H Y GUAN , L S FANG , et al . MicroRNA-374a activates Wnt/ β -catenin signaling to promote breast cancer metastasis [J]. J Clin Invest , 2013 , 123 ( 2 ): 566 - 579 .
N Gavert , ev A Ben-Ze' . β -Catenin signaling in biological control and cancer [J]. J Cell Biochem , 2010 , 102 ( 4 ): 820 - 828 .
A Eger , A Stockinger , B Schaffhauser , et al . Epithelial mesenchymal transition by c-Fos estrogen receptor activation involves nuclear translocation of beta-catenin and upregulation of beta-catenin/lymphoid enhancer binding factor-1 transcriptional activity [J]. J Cell Biol , 2000 , 148 ( 1 ): 173 - 178 .
M Zeisberg , E G Neilson . Biomarkers for epithelial-mesenchymal transitions [J]. J Clin Invest , 2009 , 119 ( 6 ): 1429 - 1437 .
L TIAN , D SHEN , X LI , et al . Ginsenoside Rg 3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4 [J]. Oncotarget , 2016 , 7 ( 2 ): 1619 - 1632 .
T HUANG , Z CHEN , L FANG . Curcumin inhibits LPS-induced EMT through downregulation of NF- κ B-Snail signaling in breast cancer cells [J]. Oncol Rep , 2013 , 29 ( 1 ): 117 - 124 .
蔡加琴 , 魏晓霞 , 黄旭慧 , 等 . 氧化苦参碱通过调控上皮间质转化抑制三阴性乳腺癌细胞侵袭转移 [J]. 中国临床药理学与治疗学 , 2018 , 23 ( 1 ): 13 - 17 .
M LI , P LI , M ZHANG , et al . Brucine suppresses breast cancer metastasis via inhibiting epithelial mesenchymal transition and matrix metalloproteinases expressions [J]. Chin J Integr Med , 2018 , 24 ( 1 ): 40 - 46 .
K H SHEN , A C LIAO , J H Hung , et al . α -Solanine inhibits invasion of human prostate cancer cell,by suppressing epithelial-mesenchymal transition and,MMPs expression [J]. Molecules , 2014 , 19 ( 8 ): 11896 - 11914 .
H Ko , Y So , H Jeon , et al . TGF- β 1 -induced epithelial-mesenchymal transition and acetylation of Smad2 and Smad3 are negatively regulated by EGCG in Human A549 lung cancer cells [J]. Cancer Lett , 2013 , 335 ( 1 ): 205 - 213 .
W Q WANG , L LIU , H C SUN , et al . Tanshinone Ⅱ A inhibits metastasis after palliative resection of hepatocellular carcinoma and prolongs survival in part via vascular normalization [J]. J Hematol Oncol , 2012 , 5 : 69 .
贺川 , 马笛 , 巩平 , 等 . 大蒜素对胰腺癌细胞上皮间质化的影响 [J]. 中国实验方剂学杂志 , 2016 , 22 ( 14 ): 130 - 134 .
李洁玭 , 秦垠 , 邹玺 , 等 . 桂皮醛通过PI3K/Akt信号通路抑制TGF- β 1 诱导的结肠癌细胞LoVo上皮间质转化 [J]. 中国实验方剂学杂志 , 2017 , 23 ( 18 ): 105 - 111 .
M Gallardo , G M Calaf . Curcumin inhibits invasive capabilities through epithelial mesenchymal transition in breast cancer cell lines [J]. Int J Oncol , 2016 , 49 ( 3 ): 1019 - 1027 .
W FAN , B Yung , P HUANG , et al . Nanotechnology for multimodal synergistic cancer therapy [J]. Chem Rev , 2017 , 117 ( 22 ): 13566 - 13638 .
S Khan , S Setua , S Kumari , et al . Superparamagnetic iron oxide nanoparticles of curcumin enhance gemcitabine therapeutic response in pancreatic cancer [J]. Biomaterials , 2019 , 208 : 83 - 97 .
N LI , Z WANG , Y T ZHANG , et al . Curcumin-loaded redox-responsive mesoporous silica nanoparticles for targeted breast cancer therapy [J]. Artif Cells Nanomed Biotechnol , 2018 , 46 ( sup2 ): 921 - 935 .
R J JU , L CHENG , X M PENG , et al . Octreotide-modified liposomes containing daunorubicin and dihydroartemisinin for treatment of invasive breast cancer [J]. Artif Cells Nanomed Biotechnol , 2018 , 46 ( sup1 ): 616 - 628 .
Y Ihara , Y Inai , M Ikezaki . Alteration of integrin-dependent adhesion and signaling in EMT-like MDCK cells established through overexpression of calreticulin [J]. J Cell Biochem , 2011 , 112 ( 9 ): 2518 - 2528 .
K Musiał , A Bargenda , D Zwolińska . Urine survivin,E-cadherin and matrix metalloproteinases as novel biomarkers in children with chronic kidney disease [J]. Biomarkers , 2015 , 20 ( 3 ): 177 - 182 .
Y ZHAO , Y TAN , T MENG , et al . Simultaneous targeting therapy for lung metastasis and breast tumor by blocking the NF- κ B signaling pathway using Celastrol-loaded micelles [J]. Drug Deliv , 2018 , 25 ( 1 ): 341 - 352 .
H WU , Q ZHONG , R ZHONG , et al . Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/d- α -tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment [J]. Int J Nanomedicine , 2016 , 11 : 6337 - 6352 .
Y ZOU , Y ZHOU , Y JIN , et al . Synergistically enhanced antimetastasis effects by honokiol-loaded pH-sensitive polymer-doxorubicin conjugate micelles [J]. ACS Appl Mater Interfaces , 2018 , 10 ( 22 ): 18585 - 18600 .
R K Verma , W YU , A Shrivastava , et al . α -Mangostin-encapsulated PLGA nanoparticles inhibit pancreatic carcinogenesis by targeting cancer stem cells in human,and transgenic (Kras G12D ,and Kras G12D /tp53R270H) mice [J]. Sci Rep , 2016 , 6 : 32743 .
C Tapeinos , M Battaglini , G Ciofani . Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases [J]. J Control Release , 2017 , 264 : 306 - 332 .
P XU , Q YIN , J SHEN , et al . Synergistic inhibition of breast cancer metastasis by silibinin-loaded lipid nanoparticles containing TPGS [J]. Int J Pharm , 2013 , 454 ( 1 ): 21 - 30 .
W LI , X LI , S LIU , et al . Gold nanoparticles attenuate metastasis by tumor vasculature normalization and,epithelial-mesenchymal transition inhibition [J]. Int J Nanomedicine , 2017 , 12 : 3509 - 3520 .
R R Arvizo , S Saha , E WANG , et al . Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle [J]. Proc Natl Acad Sci USA , 2013 , 110 ( 17 ): 6700 - 6705 .
D Dhamecha , S Jalalpure , K Jadhav . Doxorubicin-functionalized gold nanoparticles:characterization and activity against human cancer cell lines [J]. Process Biochem , 2015 , 50 ( 12 ): 2298 - 2306 .
S Balakrishnan , F A Bhat , P Raja Singh , et al . Gold nanoparticle-conjugated quercetin inhibits epithelial-mesenchymal transition,angiogenesis and invasiveness via EGFR/VEGFR-2-mediated pathway in breast cancer [J]. Cell Prolif , 2016 , 49 ( 6 ): 678 - 697 .
S N Sunil-Gowda , S Rajasowmiya , V Vadivel , et al . Gallic acid-coated sliver nanoparticle alters the expression of radiation-induced epithelial-mesenchymal transition in non-small lung cancer cells [J]. Toxicol In Vitro , 2018 , 52 : 170 - 177 .
S Bera , V De Rosa , W Rachidi , et al . Does a role for selenium in DNA damage repair explain apparent controversies in its use in chemoprevention? [J]. Mutagenesis , 2012 , 28 ( 2 ): 127 - 134 .
B Prokopczyk , J G Rosa , D Desai , et al . Chemoprevention of lung tumorigenesis induced by a mixture of benzo(a)pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by the organoselenium compound 1,4-phenylenebis(methylene)selenocyanate [J]. Cancer Lett , 2000 , 161 ( 1 ): 35 - 46 .
Jr G F Combs , W P Gray . Chemopreventive agents:selenium [J]. Pharmacol Ther , 1998 , 79 ( 3 ): 179 - 192 .
W LIU , X LI , Y S Wong , et al . Selenium nanoparticles as a carrier of 5-fluorouracil to achieve anticancer synergism [J]. ACS Nano , 2012 , 6 ( 8 ): 6578 - 6591 .
M Kumari , L Ray , M P Purohit , et al . Curcumin-loading potentiates the chemotherapeutic efficacy of selenium nanoparticles in HCT116 cells and Ehrlich' s ascites carcinoma bearing mice [J]. Eur J Pharm Biopharm , 2017 , 117 : 346 - 362 .
J X FAN , D W ZHENG , L RONG , et al . Targeting epithelial-mesenchymal transition:Metal organic network nano-complexes for preventing tumor metastasis [J]. Biomaterials , 2017 , 139 : 116 - 126 .
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