基于中医药整合药理学研究平台分析血府逐瘀汤治疗胰腺癌血瘀证的潜在活性成分及其作用机制
Analysis on potential active components and mechanism of Xuefu Zhuyu Decoction in treatment of blood stasis syndrome of pancreatic cancer based on TCMIP application
- 上海中医药杂志 2021年55卷第6期 页码：5-14
- 作者机构：
1.中国中医科学院广安门医院（北京 100053）
2.北京中医药大学（北京 100029）
3.中国中医科学院中药研究所（北京 100029）
- 作者简介：
贺忠宁，女，硕士研究生，主要从事中西医结合肿瘤学临床研究工作
张培彤，教授，博士研究生导师；E-mail：drzhangpeitong@hotmail.com。
王萍，研究员，硕士研究生导师；E-mail：hudielanwp@sina.com
- 基金信息：国家自然科学基金项目(81673797)
DOI：10.16305/j.1007-1334.2021.2011118
中图分类号：
扫 描 看 全 文
贺忠宁, 陈鸿, 杜霞, 等. 基于中医药整合药理学研究平台分析血府逐瘀汤治疗胰腺癌血瘀证的潜在活性成分及其作用机制[J]. 上海中医药杂志, 2021,55(6):5-14.
Zhongning HE, Hong CHEN, Xia DU, et al. Analysis on potential active components and mechanism of Xuefu Zhuyu Decoction in treatment of blood stasis syndrome of pancreatic cancer based on TCMIP application[J]. Shanghai Journal of Traditional Chinese Medicine, 2021,55(6):5-14.
贺忠宁, 陈鸿, 杜霞, 等. 基于中医药整合药理学研究平台分析血府逐瘀汤治疗胰腺癌血瘀证的潜在活性成分及其作用机制[J]. 上海中医药杂志, 2021,55(6):5-14. DOI： 10.16305/j.1007-1334.2021.2011118.
Zhongning HE, Hong CHEN, Xia DU, et al. Analysis on potential active components and mechanism of Xuefu Zhuyu Decoction in treatment of blood stasis syndrome of pancreatic cancer based on TCMIP application[J]. Shanghai Journal of Traditional Chinese Medicine, 2021,55(6):5-14. DOI： 10.16305/j.1007-1334.2021.2011118.
摘要
目的,2,预测血府逐瘀汤治疗胰腺癌血瘀证的潜在活性成分并初步探讨其分子机制。,方法,2,利用中医药整合药理学研究平台（TCMIP）数据库收集血府逐瘀汤的主要化学成分；利用中药靶标预测功能模块收集血府逐瘀汤的候选靶标谱；利用疾病数据库收集胰腺癌疾病基因集和血瘀证证候基因集；利用病证方关联分析模块构建“病-证-方”关联网络；利用Cytoscape软件绘制“成分-靶点-通路”网络图；利用蛋白互作网络分析数据库（STRING）构建蛋白相互作用（PPI）网络；利用生物学信息注释数据库（DAVID）进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析；再利用AutoDock 软件对主要成分和靶点进行分子对接验证。,结果,2,血府逐瘀汤治疗胰腺癌血瘀证的活性成分可能主要集中于柴胡、红花、牛膝、桔梗4味中药，主要通过40个化学成分、23个靶标、29条通路发挥其作用。,结论,2,血府逐瘀汤可能通过多种成分发挥治疗胰腺癌血瘀证的作用，通过影响MAPK3、CALM1、AKT1、HSP90AA1、CREB1等靶点，进一步影响肿瘤相关、代谢相关、免疫系统相关等通路。
Abstract
Objective,2,To predict the potential active components of Xuefu Zhuyu Decoction in the treatment of pancreatic cancer with blood stasis syndrome and to explore its molecular mechanism.,Methods,2,The main chemical constituents of Xuefu Zhuyu Decoction were collected by using the database of traditional Chinese medicine on integrative pharmacology-based research platform of traditional Chinese medicine (TCMIP) , and the candidate target spectrum of Xuefu Zhuyu Decoction was collected by using the function module of target prediction of traditional Chinese medicine, the gene sets of pancreatic cancer and blood stasis syndrome were collected by using the disease database, and the network of disease-syndrome-prescription was established based on the topological characteristic of the network. The network of "components-targets-pathways" was drawn by Cytoscape and a protein-protein interaction (PPI) network was built by STRING database. The pathway enrichment analysis of GO and KEGG was done by using DAVID database. The molecular docking of major components and targets was verified by using AutoDock.,Results,2,The active components of Xuefu Zhuyu Decoction in the treatment of pancreatic cancer with blood stasis syndrome may mainly focus on the four herbs, which are bupleurum, safflower, achyranthes bidentata and platycodon grandiflorum, and it plays its role mainly through 40 chemical components, 23 targets and 29 pathways.,Conclusion,2,Xuefu Zhuyu Decoction may play a role in the treatment of pancreatic cancer with blood stasis syndrome through a variety of components, affecting the targets of MAPK3, CALM1, AKT1, HSP90AA1 and CREB1 and so on, which further affect tumor-related pathway, metabolism-related pathway, immune system pathway, etc.
关键词
血府逐瘀汤胰腺癌血瘀证中医药整合药理学
Keywords
Xuefu Zhuyu Decoctionpancreatic cancerblood stasis syndromeintegrative pharmacology of traditional Chinese medicine
references
GOESS R, FRIESS H. A look at the progress of treating pancreatic cancer over the past 20 years[J]. Expert Rev Anticancer Ther, 2018, 18(3): 295-304.
ZENG H M, CHEN W Q, ZHENG R S, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries[J]. Lancet Glob Health, 2018, 6(5): e555-e567.
王彤，吴承玉，杨涛. 278例胰腺癌证素特征分析[J]. 中国实验方剂学杂志，2016, 22(12): 220-223.
TAO L, WANG S, ZHAO Y, et al. Pleiotropic effects of herbs characterized with blood-activating and stasis-resolving functions on angiogenesis[J]. Chin J Integr Med, 2016 22(10): 795-800.
鲁俊，陈明祺，耿艳霞，等. 益气通瘀法对多器官功能障碍综合征全身炎症反应和凝血功能影响[J]. 中国中西医结合杂志，2014, 34(1): 35-38.
刘敏，吴东雪，李晶，等. 基于药性组合的活血化瘀中药的辛苦味性效关系研究[J]. 中国中药杂志，2019, 44(2): 218-223.
KIM J M, NOH E M, SONG H K, et al. Salvia miltiorrhiza extract inhibits TPA-induced MMP-9 expression and invasion through the MAPK/AP-1 signaling pathway in human breast cancer MCF-7 cells[J]. Oncol Lett, 2017, 14(3): 3594-3600.
WU L, CAO K X, NI Z H, et al. Effects of Dahuang zhechong pill on doxorubicin-resistant SMMC-7721 xenografts in mice[J]. J Ethnopharmacol, 2018(222): 71-78.
XU H Y, ZHANG Y Q, LIU Z M, et al. ETCM: An encyclopaedia of traditional Chinese medicine[J]. Nucleic Acids Res, 2019, 47(D1): D976-D982.
ZHAO C H, LI S, ZHANG J H, et al. Current state and future perspective of cardiovascular medicines derived from natural products[J/OL]. Pharmacol Ther, 2020[2020-11-20]. https://doi.org/10.1016/2020/33039419https://doi.org/10.1016/2020/33039419.
许海玉，刘振明，付岩，等. 中药整合药理学计算平台的开发与应用[J]. 中国中药杂志，2017, 42(18): 3633-3638.
张玲玲，李毅. 阻断MAPK信号通路抗癌药的专利发展状况分析[J]. 中国新药杂志，2020, 29(19): 2178-2184
黎彩凤，张丰荣，祝娜，等. 彝族药金胃泰胶囊治疗胃肠疾病的网络药理学研究[J]. 中国中药杂志，2021, 46(4): 865-876.
YANG D Q, ZHANG Q, MA Y F, et al. Augmenting the therapeutic efficacy of adenosine against pancreatic cancer by switching the Akt/p21-dependent senescence to apoptosis[J]. EBioMedicine, 2019(47): 114-127.
BOREA P A, GESSI S, MERIGHI S, et al. Pharmacology of adenosine receptors: the state of the art[J]. Physiol Rev, 2018, 98(3): 1591-1625.
CHEN V, STAUB R E, BAGGETT S, et al. Identification and analysis of the active phytochemicals from the anti-cancer botanical extract Bezielle[J/OL]. PLoS One, 2012[2020-11-20]. https://pubmed.ncbi.nlm.nih.gov/22272282/https://pubmed.ncbi.nlm.nih.gov/22272282/.
HE X R, WANG X X, FANG J C, et al. The genus Achyranthes: A review on traditional uses, phytochemistry, and pharmacological activities[J]. J Ethnopharmacol, 2017(203): 260-278.
罗懿钒，欧阳文，唐代凤，等. 牛膝中皂苷和甾酮类物质基础及药理活性研究进展[J]. 中国现代中药，2020, 22(12): 2122-2136.
ALONSO-CASTRO A J, ORTIZ-SÁNCHAEZ E, GARCÍA-REGALADO A, et al. Kaempferitrin induces apoptosis via intrinsic pathway in HeLa cells and exerts antitumor effects[J]. J Ethnopharmacol, 2013, 145(2): 476-489.
LI X J Y, LI X Y, HUANG N N, et al. A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins[J]. Phytomedicine, 2018(50): 73-87.
BIMONTE S, CASCELLA M, LEONGITO M, et al. An overview of pre-clinical studies on the effects of (-)-epigallocatechin-3-gallate, a catechin found in green tea, in treatment of pancreatic cancer[J]. Recenti Prog Med, 2017, 108(6): 282-287.
YU G W, LUO H W, ZHANG N, et al. Loss of p53 sensitizes cells to palmitic acid-induced apoptosis by reactive oxygen species accumulation[J]. Int J Mol Sci, 2019, 20(24): 6268.
TROTT O, OLSON J A. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading[J]. J Comput Chem, 2010, 31(2): 455-461.
叶慧，张兵，蒋海伟，等. 人参皂苷Rg3的脂肪酸衍生物的合成及其体外抗肿瘤活性[J]. 食品科学，2013, 34(11): 45-48.
刘芳，刘凯，刘道洁，等. 棕榈酸对肝癌HepG2细胞自噬和凋亡的影响[J]. 山东医药，2014, 54(12): 8-9, 112-113.
陈丹丹，洪挺，王栋，等. 桔梗的化学成分及其药理作用研究概况[J]. 药品评价，2020, 17(15): 9-11.
TANIUCHI K, FURIHATA M, NAGAUMA S, et al. BCL7B, a predictor of poor prognosis of pancreatic cancers, promotes cell motility and invasion by influencing CREB signaling[J]. Am J Cancer Res, 2018, 8(3): 387-404.
WANG S, LEI Y Q, CAI Z L, et al. Girdin regulates the proliferation and apoptosis of pancreatic cancer cells via the PI3K/Akt signalling pathway[J]. Oncol Rep, 2018, 40(2): 599-608.
LU S, CHEN L L, TANG L. Upregulation of AKT1 and downregulation of AKT3 caused by dysregulation of microRNAs contributes to pathogenesis of hemangioma by promoting proliferation of endothelial cells[J]. J Cell Physiol, 2019, 234(11): 21342-21351.
SHENG W W, CHEN C P, DONG M, et al. Calreticulin promotes EGF-induced EMT in pancreatic cancer cells via Integrin/EGFR-ERK/MAPK signaling pathway[J/OL]. Cell Death Dis, 2017[2020-11-20]. https://pubmed.ncbi.nlm.nih.gov/29072694/https://pubmed.ncbi.nlm.nih.gov/29072694/.
SCHAAL C, PADMANABHAN J, CHELLAPPAN S. The role of nAChR and calcium signaling in pancreatic cancer initiation and progression[J]. Cancers (Basel), 2015, 7(3): 1447-1471.
HU C L, HART S N, POLLEY E C, et al. Association between inherited germline mutations in cancer predisposition genes and risk of pancreatic cancer[J]. JAMA, 2018, 319(23): 2401-2409.
MELLO S S, ATTARDI L D. Deciphering p53 signaling in tumor suppression[J]. Curr Opin Cell Biol, 2018(51): 65-72.
APTE R S, CHEN D S, FERRARA N. VEGF in signaling and disease: Beyond discovery and development[J]. Cell, 2019, 176(6): 1248-1264.
YAN Z L, OHUCHIDA K, FEI S, et al. Inhibition of ERK1/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis[J]. J Exp Clin Cancer Res, 2019, 38(1): 221.
ZHANG J, KINCH L N, CONG Q, et al. Assessing predictions on fitness effects of missense variants in calmodulin[J]. Hum Mutat, 2019, 40(9): 1463-1473.
TORAIH E A, ALREFAI H G, HUSSEIN M H, et al. Overexpression of heat shock protein HSP90AA1 and translocase of the outer mitochondrial membrane TOM34 in HCV-induced hepatocellular carcinoma: A pilot study[J]. Clin Biochem, 2019(63): 10-17.
LIU H, DU F, SUN L, et al. GATA6 suppresses migration and metastasis by regulating the miR-520b/CREB1 axis in gastric cancer[J]. Cell Death Dis, 2019, 10(2): 35.
0
浏览量
633
下载量
0
CSCD
7
CNKI被引量
- 网络PDF下载
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 技术支持由北京北大方正电子有限公司提供 沪ICP备13044091号
沪公网安备 31011502015228号 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies
- 总访问量：70551 今日访问量：32