The Role of Emodin in the Treatment of Bladder Cancer Based on Network Pharmacology and Experimental Verification

被引:0
作者
Liu, Fule [1 ,2 ]
Li, Jianghao [1 ,2 ]
Zhou, Boruo [1 ,2 ]
Shen, Yang [3 ]
Tang, Jingyuan [2 ]
Han, Jie [2 ]
Chen, Changpeng [1 ,2 ]
Shao, Kang [1 ,2 ]
Chen, Haojie [1 ,2 ]
Yuan, Lin [2 ]
机构
[1] Nanjing Univ Chinese Med, Clin Med Coll 1, Nanjing 210023, Peoples R China
[2] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Chinese Med, Dept Urol, Affiliated Hosp, Nanjing 210004, Peoples R China
[3] Nanjing Univ Chinese Med, Jiangsu Prov Chinese Med Hosp 2, Dept Urol, Affiliated Hosp 2, Nanjing 210017, Jiangsu, Peoples R China
关键词
Bladder cancer; emodin; network pharmacology; molecular docking; molecular mechanism; experimental verification; IN-VITRO; APOPTOSIS; CELLS; EGFR;
D O I
10.2174/0113862073294990240122140121
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Background and Purpose Emodin, a compound derived from rhubarb and various traditional Chinese medicines, exhibits a range of pharmacological actions, including anti-inflammatory, antiviral, and anticancer properties. Nevertheless, its pharmacological impact on bladder cancer (BLCA) and the underlying mechanism are still unclear. This research aimed to analyze the pharmacological mechanisms of Emodin against BLCA using network pharmacology analysis and experimental verification.Methods Initially, network pharmacology was employed to identify core targets and associated pathways affected by Emodin in bladder cancer. Subsequently, the expression of key targets in normal bladder tissues and BLCA tissues was assessed by searching the GEPIA and HPA databases. The binding energy between Emodin and key targets was predicted using molecular docking. Furthermore, in vitro experiments were carried out to confirm the predictions made with network pharmacology.Results Our analysis identified 148 common genes targeted by Emodin and BLCA, with the top ten target genes including TP53, HSP90AA1, EGFR, MYC, CASP3, CDK1, PTPN11, EGF, ESR1, and TNF. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated a significant correlation between Emodin and the PI3K-AKT pathway in the context of BLCA. Molecular docking investigations revealed a strong affinity between Emodin and critical target proteins. In vitro experiments demonstrated that Emodin inhibits T24 proliferation, migration, and invasion while inducing cell apoptosis. The findings also indicated that Emodin reduces both PI3K and AKT protein and mRNA expression, suggesting that Emodin may mitigate BLCA by modulating the PI3K-AKT signaling pathway.Conclusion This study integrates network pharmacology with in vitro experimentation to elucidate the potential mechanisms underlying the action of Emodin against BLCA. The results of this research enhance our understanding of the pharmacological mechanisms by which Emodin may be employed in treating BLCA.
引用
收藏
页码:1661 / 1675
页数:15
相关论文
共 52 条
[1]   OMIM.org: leveraging knowledge across phenotype-gene relationships [J].
Amberger, Joanna S. ;
Bocchini, Carol A. ;
Scott, Alan F. ;
Hamosh, Ada .
NUCLEIC ACIDS RESEARCH, 2019, 47 (D1) :D1038-D1043
[2]   Alkaloid from Geissospermum sericeum Benth. & Hook.f. ex Miers (Apocynaceae) Induce Apoptosis by Caspase Pathway in Human Gastric Cancer Cells [J].
Bastos, Mirian Leticia Carmo ;
Silva-Silva, Joao Victor ;
Cruz, Jorddy Neves ;
da Silva, Amanda Roberta Palheta ;
Bentaberry-Rosa, Alexandre Augusto ;
Ramos, Gisele de Costa ;
Siqueira, Jose Edson de Sousa ;
Coelho-Ferreira, Marlia Regina ;
Percario, Sandro ;
Marinho, Patricia Santana Barbosa ;
Marinho, Andrey Moacir do Rosario ;
Bahia, Marcelo de Oliveira ;
Dolabela, Maria Fani .
PHARMACEUTICALS, 2023, 16 (05)
[3]   UniProt: the universal protein knowledgebase in 2021 [J].
Bateman, Alex ;
Martin, Maria-Jesus ;
Orchard, Sandra ;
Magrane, Michele ;
Agivetova, Rahat ;
Ahmad, Shadab ;
Alpi, Emanuele ;
Bowler-Barnett, Emily H. ;
Britto, Ramona ;
Bursteinas, Borisas ;
Bye-A-Jee, Hema ;
Coetzee, Ray ;
Cukura, Austra ;
Da Silva, Alan ;
Denny, Paul ;
Dogan, Tunca ;
Ebenezer, ThankGod ;
Fan, Jun ;
Castro, Leyla Garcia ;
Garmiri, Penelope ;
Georghiou, George ;
Gonzales, Leonardo ;
Hatton-Ellis, Emma ;
Hussein, Abdulrahman ;
Ignatchenko, Alexandr ;
Insana, Giuseppe ;
Ishtiaq, Rizwan ;
Jokinen, Petteri ;
Joshi, Vishal ;
Jyothi, Dushyanth ;
Lock, Antonia ;
Lopez, Rodrigo ;
Luciani, Aurelien ;
Luo, Jie ;
Lussi, Yvonne ;
Mac-Dougall, Alistair ;
Madeira, Fabio ;
Mahmoudy, Mahdi ;
Menchi, Manuela ;
Mishra, Alok ;
Moulang, Katie ;
Nightingale, Andrew ;
Oliveira, Carla Susana ;
Pundir, Sangya ;
Qi, Guoying ;
Raj, Shriya ;
Rice, Daniel ;
Lopez, Milagros Rodriguez ;
Saidi, Rabie ;
Sampson, Joseph .
NUCLEIC ACIDS RESEARCH, 2021, 49 (D1) :D480-D489
[4]   Network analyses in systems pharmacology [J].
Berger, Seth I. ;
Iyengar, Ravi .
BIOINFORMATICS, 2009, 25 (19) :2466-2472
[5]   Virtual Combinatorial Library Screening of Quinadoline B Derivatives against SARS-CoV-2 RNA-Dependent RNA Polymerase [J].
Brogi, Simone ;
Quimque, Mark Tristan ;
Notarte, Kin Israel ;
Africa, Jeremiah Gabriel ;
Hernandez, Jenina Beatriz ;
Tan, Sophia Morgan ;
Calderone, Vincenzo ;
Macabeo, Allan Patrick .
COMPUTATION, 2022, 10 (01)
[6]   Emodin enhances antitumor effect of paclitaxel on human non-small-cell lung cancer cells in vitro and in vivo [J].
Chen, Shuifang ;
Zhang, Zeying ;
Zhang, Jianli .
DRUG DESIGN DEVELOPMENT AND THERAPY, 2019, 13 :1145-1153
[7]   TEAD4 functions as a prognostic biomarker and triggers EMT via PI3K/AKT pathway in bladder cancer [J].
Chi, Ming ;
Liu, Jiao ;
Mei, Chenxue ;
Shi, Yaxing ;
Liu, Nanqi ;
Jiang, Xuefeng ;
Liu, Chang ;
Xue, Nan ;
Hong, Hong ;
Xie, Jisheng ;
Sun, Xun ;
Yin, Bo ;
Meng, Xin ;
Wang, Biao .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2022, 41 (01)
[8]   The dual role of tumor necrosis factor-alpha (TNF-α) in breast cancer: molecular insights and therapeutic approaches [J].
Cruceriu, Daniel ;
Baldasici, Oana ;
Balacescu, Ovidiu ;
Berindan-Neagoe, Ioana .
CELLULAR ONCOLOGY, 2020, 43 (01) :1-18
[9]   Discovering Anti-Cancer Drugs via Computational Methods [J].
Cui, Wenqiang ;
Aouidate, Adnane ;
Wang, Shouguo ;
Yu, Qiuliyang ;
Li, Yanhua ;
Yuan, Shuguang .
FRONTIERS IN PHARMACOLOGY, 2020, 11
[10]   Emodin suppresses growth and invasion of colorectal cancer cells by inhibiting VEGFR2 [J].
Dai, Guoliang ;
Ding, Kang ;
Cao, Qianyu ;
Xu, Tian ;
He, Fan ;
Liu, Shijia ;
Ju, Wenzheng .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2019, 859