

浏览全部资源
扫码关注微信
1.甘肃中医药大学 药学院,兰州 730000
2.甘肃省中药药理与毒理学重点实验室,兰州 730000
Received:22 November 2021,
Published Online:11 March 2022,
Published:05 June 2022
移动端阅览
连小龙,令颖,张尚龙等.甘草有效成分抗肿瘤作用机制及联合抗肿瘤研究进展[J].中国实验方剂学杂志,2022,28(11):238-245.
LIAN Xiao-long,LING Ying,ZHANG Shang-long,et al.Anti-tumor Mechanism of Active Ingredients of Glycyrrhizae Radix et Rhizoma and Its Combined Use in Anti-tumor Treatment: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(11):238-245.
连小龙,令颖,张尚龙等.甘草有效成分抗肿瘤作用机制及联合抗肿瘤研究进展[J].中国实验方剂学杂志,2022,28(11):238-245. DOI: 10.13422/j.cnki.syfjx.20220922.
LIAN Xiao-long,LING Ying,ZHANG Shang-long,et al.Anti-tumor Mechanism of Active Ingredients of Glycyrrhizae Radix et Rhizoma and Its Combined Use in Anti-tumor Treatment: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(11):238-245. DOI: 10.13422/j.cnki.syfjx.20220922.
甘草为我国传统药材,古有“十方九草”之说。现代药理学研究表明,甘草具有抗肿瘤、抗炎杀菌、抗病毒、保肝、抗心衰、调节免疫及抗纤维化等作用。恶性肿瘤是由于多种因素引起的一种发病机制比较复杂的疾病,是全世界面临的重大难题,也是我国居民死亡的主要原因之一,相关统计数据显示,恶性肿瘤的发病率和死亡率呈不断增加趋势,且年轻化,严重威胁人们的健康安全,临床对其治疗主要以放化疗为主。目前临床多数抗肿瘤药物无选择性,在杀灭肿瘤细胞的同时对正常细胞也有严重损伤,对机体重要器官有一定损伤,且长期用药还会降低肿瘤细胞的敏感性,传统中医药辨证论治思想和多成分、多靶点的特性使其在抗肿瘤中具有一定的优势。有研究显示,中药与抗肿瘤药物联合用药在增强抗肿瘤作用的同时,还能降低毒性,故从中医药中寻找新的抗肿瘤药物成为一大热点。近年来,甘草有效成分在抗肝癌、乳腺癌、肺癌、结肠癌等肿瘤及联合抗肿瘤方面的研究取得了一定进展,在此研究基础上,通过对其诱导细胞凋亡、干扰细胞周期、诱导自噬、抑制糖酵解、调节免疫、调控miRNA和信号通路等作用机制,以及联合抗肿瘤增效减毒、增敏进行分析总结,为甘草有效成分的进一步开发和临床应用提供理论基础和研究思路。
As a traditional Chinese medicinal material, Glycyrrhizae Radix et Rhizoma has been extensively used in various formulae. According to modern pharmacological research, it has anti-tumor, anti-inflammatory, anti-viral, liver-protecting, anti-heart failure, immunoregulatory, and anti-fibrosis effects. Caused by the interaction of various factors, cancer features complex pathogenesis. It is a global challenge and one of the main causes of death in China. Statistics show that the morbidity and mortality of malignant tumors have been on the rise, particularly for the young, which threaten the health of human beings. At the moment, radiotherapy and chemotherapy are the main countermeasures. Most clinical anti-tumor drugs demonstrate non-selective toxicity. To be specific, they damage normal cells while killing tumor cells, thus injuring vital organs. In addition, long-term medication will reduce the sensitivity of tumor cells. However, traditional Chinese medicine, which is characterized by treatment based on syndrome differentiation, multiple components, and multiple targets, is superior in the treatment of tumor. Studies have shown that the combination of anti-tumor drugs with Chinese medicine can not only enhance the anti-tumor effect but also alleviate toxicity. Therefore, it has been a research hotspot to develop anti-tumor drugs based on traditional Chinese medicine. In recent years, major headway has been made in the research on active ingreddients of Glycyrrhizae Radix et Rhizoma in anti-liver cancer, anti-breast cancer, anti-lung cancer, and anti-colon cancer and the combination with other drugs for anti-tumor. On this basis, we summarized the mechanisms of active ingredients of Glycyrrhizae Radix et Rhizoma in inducing apoptosis, interfering with cell cycle, inducing autophagy, inhibiting glycolysis, regulating immunity, and modulating miRNA and signaling pathways, as well as the combination with other drugs in anti-tumor efficiency, toxicity reduction, and sensitivity enhancement, hoping to lay a theoretical basis for the further development and clinical application of active ingredients of Glycyrrhizae Radix et Rhizoma.
国家药典委员会 . 中华人民共和国药典:一部 [J]. 北京 : 中国医药科技出版社 , 2020 : 88 .
HE J B , CHEN K , HU Z M , et al . UGT73F17,a new glycosyltransferase from Glycyrrhiza uralensis ,catalyzes the regiospecific glycosylation of pentacyclic triterpenoids [J]. Chem Commun(Camb) , 2018 , 54 ( 62 ): 8594 - 8597 .
FU Y , CHEN J , LI Y J , et al . Antioxidant and anti-inflammatory activities of six flavonoids separated from licorice [J]. Food Chem , 2013 , 141 ( 2 ): 1063 - 1071 .
SONG W , QIAO X , CHEN K , et al . Biosynthesis-based quantitative analysis of 151 secondary metabolites of licorice to differentiate medicinal Glycyrrhiza species and their hybrids [J]. Anal Chem , 2017 , 89 ( 5 ): 3146 - 3153 .
冷晶 , 朱云祥 , 陈璐琳 , 等 . 甘草中2个新三萜皂苷 [J]. 中草药 , 2015 , 46 ( 11 ): 1576 - 1582 .
方诗琦 , 冷康 , 段金廒 , 等 . 甘草药渣中黄酮类成分及其抗氧化活性的研究 [J]. 中成药 , 2015 , 37 ( 11 ): 2443 - 2448 .
刘芬 , 倪慧 , 卿德刚 , 等 . 甘草药渣化学成分的分离与鉴定 [J]. 中国药物化学杂志 , 2011 , 21 ( 4 ): 312 - 314 .
孙宇 , 卿德刚 , 张娟 , 等 . 胀果甘草中查尔酮类物质对结肠癌的作用研究 [J]. 中国民族医药杂志 , 2020 , 26 ( 1 ): 29 - 31 .
范敏慧 , 何晓其 , 吴亚萍 . 新甘草酚对HepG2人肝癌细胞增殖的影响及机制研究 [J]. 浙江中西医结合杂志 , 2020 , 30 ( 12 ): 972 - 976 .
彭江华 , 马建永 . 甘草次酸对人乳腺癌MDA-MB-231细胞的影响研究 [J]. 中国临床药理学杂志 , 2019 , 35 ( 20 ): 2616 - 2619 .
MAN Q , DENG Y , LI P J , et al . Licorice ameliorates cisplatin-induced hepatotoxicity through antiapoptosis, antioxidative stress, anti-inflammation, and acceleration of metabolism [J]. Front Pharmacol , 2020 , 11 : 563750 . doi: 10.3389/fphar.2020.563750 http://dx.doi.org/10.3389/fphar.2020.563750 .
CHENG X , FERRELL J E J R . Apoptosis propagates through the cytoplasm as trigger waves [J]. Science , 2018 , 361 ( 6402 ): 607 - 612 .
ZARE Z , ZARBAKHSH S , TEHRANI M , et al . Paraoxon-induced damage in rat hippocampus is association with alterations in the expression of apoptosis-related proteins [J]. Pestic Biochem Physiol , 2020 , doi: 10.1016/ j.pestbp.2020.104580 http://dx.doi.org/10.1016/j.pestbp.2020.104580 .
PFEFFER C , SINGH A . Apoptosis : a target for anticancer therapy [J]. Int J Mol Sci , 2018 , 19 ( 2 ): 448 . doi: 10.3390/ ijms19020448 http://dx.doi.org/10.3390/ijms19020448 .
PISTRITTO G , D TRISCIUOGLIO , CECI C , et al . Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies [J]. Aging , 2016 , 8 ( 4 ): 603 - 619 .
WU R , TANG S , WANG M , et al . MicroRNA-497 induces apoptosis and suppresses proliferation via the Bcl-2/Bax- Caspase9-Caspase3 pathway and cyclin D 2 protein in HUVECs [J]. PLoS One , 2016 , 11 ( 12 ): e0167052 .
刘景华 , 赵阳 , 李宾 , 等 . 甘草次酸对胃癌细胞SGC7901增殖、凋亡及PI3K-Akt-mTOR通路的影响 [J]. 药物评价研究 , 2020 , 43 ( 12 ): 2444 - 2449 .
BROWN J M , ATTARDI L D . The role of Apoptosis in cancer development and treatment response [J]. Nat Rev Cancer , 2005 , 5 ( 3 ): 231 - 237 .
ZHENG C , LIU T , LIU H , et al . Role of Bcl-2 family proteins in apoptosis and its regulation by nutrients [J]. Curr Protein Pept Sci , 2020 , 21 ( 8 ): 799 - 806 .
袁永贵 , 张夏炎 , 朱晓俊 , 等 . 甘草查尔酮A对人乳腺癌MDA-MB-231细胞凋亡的影响 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 20 ): 95 - 100 .
WENZEL E S , SINGH A T K . Cell-cycle checkpoints and aneuploidy on the path to cancer [J]. In Vivo , 2018 , 32 ( 1 ): 1 - 5 .
黄尚校 , 李春君 , 黄剑锋 , 等 . 光甘草定对宫颈癌Hela细胞增殖、侵袭和凋亡的影响及其机制 [J]. 现代肿瘤医学 , 2020 , 28 ( 19 ): 3289 - 3293 .
PARZYCH K R , KLIONSKY D J . An overview of autophagy:morphology,mechanism,and regulation [J]. Antioxid Redox Signal , 2014 , 20 ( 3 ): 460 - 473 .
WILDE L , TANSON K , CURRY J , et al . Autophagy in cancer:A complex relationship [J]. Biochem J , 2018 , 475 ( 11 ): 1939 - 1954 .
郑方静 , 赖红华 , 赖晓兰 , 等 . 微小RNA-216a调控JAK2/STAT3通路对鼻咽癌细胞增殖、侵袭、自噬及血管生成的影响 [J]. 肿瘤学杂志 , 2021 , 27 ( 11 ): 905 - 914 .
李霄 , 张玄 , 张卓超 , 等 . 甘草甜素体外诱导肝癌细胞MHCC97-H自噬性死亡的实验 [J]. 中华肝胆外科杂志 , 2018 , 24 ( 2 ): 116 - 121 .
张荣芳 , 王春玲 , 李申 , 等 . 甘草素通过影响鼻咽癌CNE-2细胞的自噬增强其放疗敏感性 [J]. 中国肿瘤生物治疗杂志 , 2018 , 25 ( 06 ): 601 - 606 .
TANG Z H , LI T , CHANG L L , et al . Glycyrrhetinic acid triggers a protective autophagy by activation of extracellular regulated protein kinases in hepatocellular carcinoma cells [J]. J Agric Food Chem , 2014 , 62 ( 49 ): 11910 - 11916 .
WILDE L , ROCHE M , DOMINGO-VIDAL M , et al . Metabolic coupling and the reverse warburg effect in cancer:Implications for novel biomarker and anticancer agent development [J]. Semin Oncol , 2017 , 44 ( 3 ): 198 - 203 .
BARTRONS R , CARO J.Hypoxia , glucose metabolism and the Warburgs effect [J]. J Bioenerg Biomembr , 2007 , 39 ( 3 ): 223 - 229 .
李璐佳 , 李国文 , 谢燕 . 光甘草定和槲皮素对乳腺癌细胞能量代谢的调控作用 [J]. 中国中药杂志 , 2019 , 44 ( 17 ): 3786 - 3791 .
杨楠 , 贾晓斌 , 张振海 , 等 . 黄酮类化合物抗肿瘤活性及机制研究进展 [J]. 中国中药杂志 , 2015 , 40 ( 3 ): 373 - 381 .
CLENET M L , GAGNON F , MORATALLA A C , et al . Peripheral human CD4 + CD8 + T lymphocytes exhibit a memory phenotype and enhanced responses to IL-2,IL-7 and IL-15 [J]. Sci Rep , 2017 , 7 ( 1 ): 11612 .
王娜 , 张霞 . 甘草甜素调节U14宫颈癌小鼠免疫功能及诱导凋亡的作用 [J]. 食品工业科技 , 2021 , 42 ( 23 ): 370 - 376 .
PISHKARI S , PARYAN M , HASHEMI M , et al . The role of microRNAs in different types of thyroid carcinoma: A comprehensive analysis to find new miRNA supplementary therapies [J]. J Endocrinol Invest , 2018 , 41 ( 3 ): 269 - 283 .
王中琴 , 胡青 , 张晋锋 . 甘草提取物通过调控miR-212-5p/BCL2L2基因抑制甲状腺肿瘤细胞的增殖、迁移和侵袭 [J]. 中华细胞与干细胞杂志:电子版 , 2021 , 11 ( 1 ): 25 - 33 .
YU Y , JIAXIN T , YI G , et al . MicroRNA-216b-5p functions as a tumor-suppressive RNA by targeting TPT1 in pancreatic cancer cells [J]. J Cancer , 2017 , 8 ( 14 ): 2854 - 2865 .
陈钰龙 , 王华启 , 张莉蓉 . 甘草素通过调控miR-216b-5p对肺腺癌细胞增殖凋亡及化疗敏感性的作用研究 [J]. 中国药理学通报 , 2021 , 37 ( 11 ): 1559 - 1564 .
HAWES C , KIVINIEMI P , KRIECHBAUMER V . The endoplasmic reticulum:A dynamic and well-connected organelle [J]. J Integr Plant Biol , 2015 , 57 ( 1 ): 50 - 62 .
HETZ C , PAPA F R . The unfolded protein response and cell fate control [J]. Mol Cell , 2018 , 69 ( 2 ): 169 - 181 .
周鑫 , 于睿 , 林萍 . 参附汤通过Ca 2+ SERCA2a调控心力衰竭大鼠内质网应激改善心肌损伤研究 [J]. 中华中医药学刊 , 2021 , 39 ( 9 ):36-40, 260 - 261 .
KIM I , XU W , REED J C . Cell death and endoplasmic reticulum stress:disease relevance and therapeutic opportunities [J]. Nat Rev Drug Discov , 2008 , 7 ( 12 ): 1013 - 1030 .
TANIGUCHI K , KARIN M . NF-kappa B,inflammation,immunity and cancer:coming of age [J]. Nat Rev Immunol , 2018 , 18 ( 5 ): 309 - 324 .
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- κ B信号通路的影响 [J]. 天然产物研究与开发 , 2018 , 30 ( 5 ): 847 - 855 .
TONG X S , GU J H , SONG R , et al . Osteoprotegerin inhibit osteoclast differentiation and bone resorption by enhancing autophagy via AMPK/mTOR/p70S6K signaling pathway in vitro [J]. J Cell Biochem , 2019 , 120 ( 2 ): 1630 - 1642 .
HUANG X , WU H , JIANG R , et al . The antidepressant effects of α -tocopherol are related to activation of autophagy via the AMPK/mTOR pathway [J]. Eur J Pharmaclo , 2018 , doi: 10.1016/j.ejphar. 2018.05.020 http://dx.doi.org/10.1016/j.ejphar.2018.05.020 .
张炜 , 耿玉东 , 王书斌 , 等 . 甘草素通过AMPK/mTOR通路对人口腔鳞癌细胞放疗敏感性的作用研究 [J]. 中华老年口腔医学杂志 , 2021 , 19 ( 5 ): 271 - 276 .
WULLSCHLEGER S , LOEWITH R , HALL M N . TOR signaling in growth and metabolism [J]. Cell , 2006 , 124 ( 3 ): 471 - 484 .
HAISSAGUERRE M , COTA D . Role of the mTOR pathway in the central regulation of energy balance [J]. Biol Aujourdhui , 2015 , 209 ( 4 ): 295 - 307 .
肖昊 , 谭碧娥 , 吴苗苗 , 等 . mTOR信号通路调节细胞能量代谢的机制 [J]. 中国科学:生命科学 , 2015 , 45 ( 11 ): 1124 - 1131 .
LAWRENCE J , NHO R . The role of the mammalian target of rapamycin(mTOR) in pulmonary fibrosis [J]. Int J Mol Sci , 2018 , 19 ( 3 ): 778 .
XING X F , ZHANG L H , WEN X Z , et al . PP242 suppresses cell proliferation,metastasis,and angiogenesis of gastric cancer through inhibition of the PI3K/Akt/mTOR pathway [J]. Anticancer Drugs , 2014 , 25 ( 10 ): 1129 - 1140 .
YERRA V G , KALVALA A K , Kumar A . Isoliquiritigenin reduces oxidative damage and alleviates mitochondrial impairment by SIRT1 activation in experimental diabetic Neuropathy [J]. J Nutr Biochem , 2017 , 47 ( 1 ): 41 - 52 .
BABA M , ASANO R , TAKIGAMI I , et al . Studies on cancer chemoprevention by traditional folk medicinesⅩⅩⅤ. Inhibitory effect of isoliquiritigenin on azoxymethane-induced murine colon aberrant crypt focus formation and carcinogenesis [J]. Biol Pharm Bull , 2002 , 25 ( 2 ): 247 - 250 .
傅丹青 , 陈超 , 侯晓丽 , 等 . 绞股蓝总皂苷对高糖环境下小鼠肾脏足细胞自噬及mTOR /4EBP1/P70S6K信号通路的影响 [J]. 中华中医药杂志 , 2021 , 36 ( 5 ): 2499 - 2502 .
姬超 , 康媛 , 张月宁 , 等 . 异甘草素对宫颈癌细胞生物学特性及mTOR/P70S6K信号通路的影响 [J]. 中国妇幼保健 , 2021 , 36 ( 11 ): 2630 - 2633 .
RAMEH L E , CANTLEY L C . The role of phosphoinositide 3-kinase lipid produccts in cell function [J]. J Biol Chem , 1999 , 274 ( 13 ): 8347 - 8350 .
STAL O , PEREZ-TENORIO G , AKERBERG L , et al . Akt kinases in breast cancer and the results of adjuvanttherapy [J]. Breast Cancer Res , 2003 , 5 ( 2 ): R37 - R44 .
KENNEDY S G , KANDEL E S , CROSS T K , et al . Akt/protein kinase B inhibits cell death by preventing the release of cytochrome C from mitochondria [J]. Mol Cell Biol , 1999 , 19 ( 8 ): 5800 - 5810 .
ERSAHIN T , TUNCBAG N , CETIN-ATALAY R . The PI3K/Akt/mTOR interactive pathway [J]. Mol Biosyst , 2015 , 11 ( 7 ): 1946 - 1954 .
HAN X , XUE R , YUAN H J , et al . MicroRNA-21 plays a pivotal role in the oocyte-secreted factor-induced suppression of cumulus cell apoptosis [J]. Biol Reprod , 2017 , 96 ( 6 ): 1167 - 1180 .
辛红 , 孙鹏然 , 宋鹏 , 等 . 异甘草素对人肾透明细胞癌786-O细胞抗癌作用及分子机制 [J]. 中国实验方剂学杂志 , 2019 , 25 ( 12 ): 83 - 89 .
邓溪川 , 刘璐 , 王占利 , 等 . 甘草苷调控PI3K/Akt/m-TOR信号通路对口腔鳞状细胞癌细胞及裸鼠移植瘤小鼠的作用研究 [J]. 实用口腔医学杂志 , 2021 , 37 ( 1 ): 10 - 14 .
王超 , 李元滨 . 中药复方多靶点逆转肺癌化疗多药耐药机制效应的研究进展 [J]. 中华中医药杂志 , 2019 , 34 ( 2 ): 688 - 691 .
陈岩岩 , 周淑娟 , 夏玉朝 , 等 . 甘草黄酮联合顺铂对Lewis肺癌荷瘤小鼠的影响 [J]. 中成药 , 2020 , 42 ( 4 ): 1035 - 1037 .
MAYEKAR M K , BIVONA T G . Current landscape of targeted therapy in lung cancer [J]. Clin Pharmacol Ther , 2017 , 102 ( 5 ): 757 - 764 .
廖奎 , 王志令 , 彭志平 , 等 . 双氢青蒿素对肺癌细胞株H1299增殖与放疗增敏的影响 [J]. 中国免疫学杂志 , 2015 , 31 ( 2 ): 185 - 188 .
王勇 , 黄大兵 , 沈夏波 , 等 . 甘草素调控WIG-1基因对肺癌细胞增殖、细胞凋亡及放疗敏感性影响的研究 [J]. 中国免疫学杂志 , 2020 , 36 ( 10 ): 1194 - 1200 .
SIEGEL R L , MILLER K D , Jemal A . Cancer statistics,2020 [J]. CA Cancer J Clin , 2020 , 70 ( 1 ): 7 - 30 .
BRAY F , FERLAY J , SOERJOMATARAM I , et al . Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Carcer J Clin , 2018 , 68 ( 6 ): 394 - 424 .
王璇 . 中医药治疗恶性肿瘤淋巴结转移思路初探 [J]. 新中医 , 2021 , 53 ( 22 ): 155 - 159 .
刘学伟 , 娄彦妮 , 冯哲 , 等 . 从国家自然科学基金资助项目浅谈中医药在恶性肿瘤治疗中的增效减毒作用研究现状 [J]. 中国中药杂志 , 2022 , 47 ( 1 ): 253 - 258 .
张晨 , 李娜 , 钟赣生 , 等 . 十八反中甘草物种的本草考证 [J]. 中草药 , 2021 , 52 ( 20 ): 6425 - 6430 .
郑云枫 , 魏娟花 , 冷康 , 等 . 甘草属 Glycyrrhiza L.植物资源化学及利用研究进展 [J]. 中国现代中药 , 2015 , 17 ( 10 ): 1096 - 1108 .
0
Views
23
下载量
6
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621