

浏览全部资源
扫码关注微信
安徽中医药大学,合肥 230012
Received:22 March 2020,
Published Online:24 July 2020,
Published:20 November 2020
移动端阅览
丁芮,王翔,周鹏等.小陷胸汤中抗肿瘤作用有效成分及其机制研究进展[J].中国实验方剂学杂志,2020,26(22):186-192.
DING Rui,WANG Xiang,ZHOU Peng,et al.Research Progress on Antitumor Active Components and Mechanism of Xiao Xianxiongtang[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(22):186-192.
丁芮,王翔,周鹏等.小陷胸汤中抗肿瘤作用有效成分及其机制研究进展[J].中国实验方剂学杂志,2020,26(22):186-192. DOI: 10.13422/j.cnki.syfjx.20201981.
DING Rui,WANG Xiang,ZHOU Peng,et al.Research Progress on Antitumor Active Components and Mechanism of Xiao Xianxiongtang[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(22):186-192. DOI: 10.13422/j.cnki.syfjx.20201981.
肿瘤是严重危害人类健康的疾病之一,如何有效治疗该疾病是当今医学领域中亟需解决的重要问题之一。目前,针对肿瘤的治疗大多采用放射性治疗及化学药物治疗方法,虽疗效明显但副作用较大,而中医药以其独特的辨证论治体系与整体观念,在治疗肿瘤方面具有多途径、多层次、多环节、多靶点且毒副作用小等优势,可充分调动机体免疫防疫机制,已成为抗肿瘤药物重点的研发对象。大量研究表明小陷胸汤及其有效成分抗肿瘤疗效明显,众多医家将小陷胸汤及其加减化裁方用于肿瘤的临床治疗,具有广泛的实践基础,且相关药理研究亦证实了该方的有效性,但其抗肿瘤有效成分及其作用机制尚缺乏系统的归纳总结。现以小陷胸汤中生物碱类、酮类、甾醇类及酚类成分为出发点,以抑制肿瘤细胞增殖与侵袭迁移、诱导肿瘤细胞凋亡和自噬、阻滞肿瘤细胞周期、增强肿瘤细胞敏感性、抑制肿瘤血管生成以及调节免疫抑制肿瘤微环境为主要内容,从药物的成分到作用、作用到机制2条途径进行梳理,对小陷胸汤中抗肿瘤作用的有效成分、主要的作用靶点、干预肿瘤发展过程的机制等进行综述,以期为后续小陷胸汤抗肿瘤研究与开发提供新的思路。
Tumor is one of the diseases that seriously endanger human health, and how to treat tumor effectively is still one of the important problems in the field of medicine. At present, most of the radiotherapies and chemical drugs for cancer have serious side effect despite of an obvious efficacy. With a unique syndrome differentiation treatment system and overall concept, traditional Chinese medicine has become the key research and development object of antitumor drugs due to many advantages, such as multiple channels, multiple levels, multiple links, multiple targets and less toxicity, and could can fully mobilize the immune and epidemic prevention mechanism of the body. A large number of studies have shown that Xiao Xianxiongtang and its effective ingredients have obvious antitumor effect. Many doctors have applied Xiao Xianxiongtang and modified formulas in clinical treatment of tumors, and relevant pharmacological studies have also confirmed the effectiveness of this formula, but with a lack of systematic summary of its effective ingredients and its mechanism of action. Now, with alkaloids, ketones, sterols and phenols in Xiao Xianxiongtang as the starting point, this study mainly focuses on inhibition of tumor cell proliferation, invasion and migration, induction of tumor cell apoptosis and autophagy, inhibition of tumor cell cycle, enhancement of tumor cell sensitivity, inhibition of tumor angiogenesis and regulation of immunosuppressive tumor microenvironment from two ways to sort out composition, function and mechanism of drugs. In this paper, effective components, main targets and mechanism of intervention in the tumor development of Xiao Xianxiongtang were reviewed, in order to provide a new idea for subsequent antitumor research and development of this prescription.
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 Cancer J Clin , 2018 , 68 ( 6 ): 394 - 424 .
姬颖华 , 杨晓煜 , 王荦楠 . 中药复方胃肠安对人SGC-7901胃癌细胞裸鼠移植瘤的抑制作用及机制研究 [J]. 中药新药与临床药理 , 2015 , 26 ( 2 ): 160 - 164 .
李文畅 , 沈洪昇 , 白雪 , 等 . 温阳通窍中药复方对大鼠脑胶质瘤作用机制的体内实验研究 [J]. 天津中医药大学学报 , 2015 , 34 ( 3 ): 156 - 159 .
周蕾 , 刘嘉湘 . 刘嘉湘运用小陷胸汤治疗肿瘤相关症状举隅 [J]. 辽宁中医杂志 , 2016 , 43 ( 3 ): 617 - 619 .
周佳静 , 贾英杰 . 贾英杰教授运用小陷胸汤合苇茎汤治疗肺癌并发恶性胸腔积液经验举隅 [J]. 西部中医药 , 2012 , 25 ( 4 ): 31 - 33 .
ABRAMS S L , FOLLO M Y , STEELMAN L S , et al . Abilities of berberine and chemically modified berberines to inhibit proliferation of pancreatic cancer cells [J]. Adv Biol Regul , 2019 , 71 : 172 - 182 .
HUANG C , WANG X L , QI F F , et al . Berberine inhibits epithelial-mesenchymal transition and promotes apoptosis of tumour-associated fibroblast-induced colonic epithelial cells through regulation of TGF- β signalling [J]. J Cell Commun Signal , 2020 , 14 ( 6 ): 53 - 66 .
GONG C , HU X , XU Y , et al . Berberine inhibits proliferation and migration of colorectal cancer cells by downregulation of GRP78 [J]. Anticancer Drugs , 2020 , 31 ( 2 ): 141 - 149 .
MA W , ZHU M , ZHANG D , et al . Berberine inhibits the proliferation and migration of breast cancer ZR-75-30 cells by targeting Ephrin-B 2 [J]. Phytomedicine , 2017 , 25 : 45 - 51 .
ZHAO Y , CUI L , PAN Y , et al . Berberine inhibits the chemotherapy-induced repopulation by suppressing the arachidonic acid metabolic pathway and phosphorylation of FAK in ovarian cancer [J]. Cell Proliferation , 2017 , doi: 10.1111/cpr.12393 http://dx.doi.org/10.1111/cpr.12393 .
MURTHY K N C , JAYAPRAKASHA G K , PATIL B S . Cytotoxicity of obacunone and obacunone glucoside in human prostate cancer cells involves Akt-mediated programmed cell death [J]. Toxicology , 2015 , 329 : 88 - 97 .
CHAI F N , MA W Y , ZHANG J , et al . Coptisine from Rhizoma Coptidis exerts an anti-cancer effect on hepatocellular carcinoma by up-regulating miR-122 [J]. Biomed Pharmacother , 2018 , 103 : 1002 - 1011 .
孙怡 , 顾君 . 槲皮素抑制乳腺癌细胞迁移侵袭及分子机制研究 [J]. 中国中药杂志 , 2015 , 40 ( 6 ): 1144 - 1150 .
TAN H Y , WANG N , MAN K , et al . Autophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin [J]. Cell Death Dis , 2015 , doi: 10.1038/cddis.2015.271 http://dx.doi.org/10.1038/cddis.2015.271 .
林明珠 , 赵岩 , 蔡恩博 , 等 . β -谷甾醇对H (22)荷瘤小鼠体内抗肿瘤作用 [J]. 中国公共卫生 , 2017 , 33 ( 12 ): 1797 - 1800 .
ALI H , DIXIT S , ALI D , et al . Isolation and evaluation of anticancer efficacy of stigmasterol in a mouse model of DMBA-induced skin carcinoma [J]. Drug Des Devel Ther , 2015 , 9 : 2793 - 2800 .
LIU J , WEN X , LIU B , et al . Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP-2 and MMP-9 [J]. Mol Med Rep , 2016 , 13 ( 3 ): 2401 - 2408 .
HUANG Y C , LEE P C , WANG J J , et al . Anticancer effect and mechanism of hydroxygenkwanin in oral squamous cell carcinoma [J]. Front Oncol , 2019 , 9 : 911 .
WANG Y F , XU Y L , TANG Z H , et al . Baicalein induces Beclin 1- and extracellular signal-regulated kinase-dependent autophagy in ovarian cancer cells [J]. Am J Chin Med , 2017 , 45 ( 1 ): 123 - 136 .
YANG X , JIANG J , ZHANG C , et al . Baicalein restrains proliferation, migration, and invasion of human malignant melanoma cells by down-regulating colon cancer associated transcript-1 [J]. Braz J Med Biol Res , 2019 , doi: 10.1590/1414-431X20198934 http://dx.doi.org/10.1590/1414-431X20198934 .
WANG Q , XU H , ZHAO X . Baicalin inhibits human cervical cancer cells by suppressing protein kinase C/signal transducer and activator of transcription (PKC/STAT3) signaling pathway [J]. Med Sci Monit , 2018 , 24 : 1955 - 1961 .
DIAO X , YANG D , CHEN Y , et al . Baicalin suppresses lung cancer growth by targeting PDZ-binding kinase/T-LAK cell-originated protein kinase [J]. Biosci Rep , 2019 , doi: 10.1042/BSR20181692 http://dx.doi.org/10.1042/BSR20181692 .
曹张琦 . β -谷甾醇协同吉西他滨通过诱导凋亡和抑制上皮间质转化的抗胰腺癌作用研究 [D]. 兰州 : 兰州大学 , 2019 .
CHEN Q Q , SHI J M , DING Z , et al . Berberine induces apoptosis in non-small-cell lung cancer cells by upregulating miR-19a targeting tissue factor [J]. Cancer Manag Res , 2019 , 11 : 9005 - 9015 .
刘虹 , 邵荣光 . 自噬在肿瘤发生与发展过程中的调节作用 [J]. 药学学报 , 2016 , 51 ( 1 ): 23 - 28 .
陈兰芳 , 肖亮 , 杨军平 . 细胞自噬的分子机制及其功能 [J]. 实验与检验医学 , 2014 , 32 ( 2 ): 157 - 163 .
ZHUO Y , CHEN Q , CHEN B , et al . Berberine promotes antiproliferative effects of epirubicin in T24 bladder cancer cells by enhancing apoptosis and cell cycle arrest [J]. Int J Clin Pharmacol Ther , 2017 , 55 ( 1 ): 32 - 40 .
CHIDAMBARA MURTHY K N , JAYAPRAKASHA G K , PATIL B S . Apoptosis mediated cytotoxicity of citrus obacunone in human pancreatic cancer cells [J]. Toxicol In Vitro , 2011 , 25 ( 4 ): 859 - 867 .
TEEKARAMAN D , ELAYAPILLAI S P , VISWANATHAN M P , et al . Quercetin inhibits human metastatic ovarian cancer cell growth and modulates components of the intrinsic apoptotic pathway in PA-1cell line [J]. Chem Biol Interact , 2019 , 300 : 91 - 100 .
SOOK S H , LEE H J , KIM J H , et al . Reactive oxygen species-mediated activation of AMP-activated protein kinase and c-Jun N -terminal kinase plays a critical role in beta-sitosterol-induced apoptosis in multiple myeloma U266 cells [J]. Phytother Res , 2014 , 28 ( 3 ): 387 - 394 .
OAK C , KHALIFA A O , ISALI I , et al . Diosmetin suppresses human prostate cancer cell proliferation through the induction of apoptosis and cell cycle arrest [J]. Int J Oncol , 2018 , 53 ( 2 ): 835 - 843 .
WANG C , LI S , REN H , et al . Anti-proliferation and pro-apoptotic effects of diosmetin via modulating cell cycle arrest and mitochondria-mediated intrinsic apoptotic pathway in MDA-MB-231 cells [J]. Med Sci Monit , 2019 , 25 : 4639 - 4647 .
KOOSHA S , MOHAMED Z , SINNIAH A , et al . Evaluation of anti-tumorigenic effects of diosmetin against human colon cancer xenografts in athymic nude mice [J]. Molecules , 2019 , 24 ( 14 ): 2522 .
JIANG L , SONG H , GUO H , et al . Baicalein inhibits proliferation and migration of bladder cancer cell line T24 by down-regulation of microRNA-106 [J]. Biomed Pharmacother , 2018 , 107 : 1583 - 1590 .
WANG M , QIU S , QIN J . Baicalein induced apoptosis and autophagy of undifferentiated thyroid cancer cells by the ERK/PI3K/Akt pathway [J]. Am J Transl Res , 2019 , 11 ( 6 ): 3341 - 3352 .
YAN W , MA X , ZHAO X , et al . Baicalein induces apoptosis and autophagy of breast cancer cells via inhibiting PI3K/Akt pathway in vivo and vitro [J]. Drug Des Devel Ther , 2018 , 12 : 3961 - 3972 .
HAN B , JIANG P , LI Z , et al . Coptisine-induced apoptosis in human colon cancer cells (HCT-116) is mediated by PI3K/Akt and mitochondrial-associated apoptotic pathway [J]. Phytomedicine , 2018 , 48 : 152 - 160 .
SEDKY N K , EL GAMMAL Z H , WAHBA A E , et al . The molecular basis of cytotoxicity of alpha-spinasterol from Ganoderma resinaceum : induction of apoptosis and overexpression of p53 in breast and ovarian cancer cell lines [J]. J Cell Biochem , 2018 , 119 ( 5 ): 3892 - 3902 .
ZHANG Y L , ZHANG X , MIAO X Z , et al . Coptisine suppresses proliferation and inhibits metastasis in human pancreatic cancer PANC-1 cells [J]. J Asian Nat Prod Res , 2020 , 22 ( 5 ): 452 - 463 .
RAO P C , BEGUM S , SAHAI M , et al . Coptisine-induced cell cycle arrest at G 2 /M phase and reactive oxygen species-dependent mitochondria-mediated apoptosis in non-small-cell lung cancer A549 cells [J]. Tumour Biol , 2017 , doi: 10.1177/1010428317694565 http://dx.doi.org/10.1177/1010428317694565 .
KEDHARI SUNDARAM M , RAINA R , AFROZE N , et al . Quercetin modulates signaling pathways and induces apoptosis in cervical cancer cells [J]. Biosci Rep , 2019 , doi: 10.1042/BSR20190720 http://dx.doi.org/10.1042/BSR20190720 .
WANG Z , MA L , SU M , et al . Baicalin induces cellular senescence in human colon cancer cells via upregulation of DEPP and the activation of Ras/Raf/MEK/ERK signaling [J]. Cell Death Dis , 2018 , 9 ( 2 ): 217 .
CHAKRAVARTHY D , MUNOZ A R , SU A , et al . Palmatine suppresses glutamine-mediated interaction between pancreatic cancer and stellate cells through simultaneous inhibition of survivin and COL1A1 [J]. Cancer Lett , 2018 , 419 : 103 - 115 .
LAN C Y , CHEN S Y , KUO C W , et al . Quercetin facilitates cell death and chemosensitivity through RAGE/PI3K/Akt/mTOR axis in human pancreatic cancer cells [J]. J Food Drug Anal , 2019 , 27 ( 4 ): 887 - 896 .
CELANO M , MAGGISANO V , BULOTTA S , et al . Quercetin improves the effects of sorafenib on growth and migration of thyroid cancer cells [J]. Endocrine , 2020 , 67 ( 6 ): 496 - 498 .
XU Z , YAN Y , XIAO L , et al . Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt signaling pathway [J]. PLoS One , 2017 , doi: 10.1371/journal.pone.0175977 http://dx.doi.org/10.1371/journal.pone.0175977 .
KANGSAMAKSIN T , CHAITHONGYOT S , WOOTTHICHAIRANGSAN C , et al . Lupeol and stigmasterol suppress tumor angiogenesis and inhibit cholangiocarcinoma growth in mice via downregulation of tumor necrosis factor-alpha [J]. PLoS One , 2017 , doi: 10.1371/journal.pone.0189628 http://dx.doi.org/10.1371/journal.pone.0189628 .
CONSTANTINOU C , CHARALAMBOUS C , KANAKIS D . Vitamin E and cancer: an update on the emerging role of gamma and delta tocotrienols [J]. Eur J Nutr , 2020 , 59 ( 3 ): 845 - 857 .
王盛典 , 贾明明 . 肿瘤免疫微环境在肿瘤常规治疗效应中的作用 [J]. 中国肿瘤生物治疗杂志 , 2012 , 19 ( 3 ): 229 - 238 .
ZHAO R , CHEN Z , JIA G , et al . Protective effects of diosmetin extracted from Galium verum L. on the thymus of U14-bearing mice [J]. Can J Physiol Pharmacol , 2011 , 89 ( 9 ): 665 - 673 .
ZHANG J , SHEN L , LI X , et al . Nanoformulated codelivery of quercetin and alantolactone promotes an antitumor response through synergistic immunogenic cell death for microsatellite-stable colorectal cancer [J]. ACS Nano , 2019 , 13 ( 11 ): 12511 - 12524 .
0
Views
16
下载量
4
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621