Investigating mechanism of cinobufagin in gastric cancer treatment based on network pharmacology and bioinformatics

ZHANG Hao; LI Xue-Yan; LI Ling-Min; JIAN Bai-Yu

doi:10.16098/j.issn.0529-1356.2025.01.006

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Acta Anatomica Sinica ›› 2025, Vol. 56 ›› Issue (1) : 43-49. DOI: 10.16098/j.issn.0529-1356.2025.01.006

Investigating mechanism of cinobufagin in gastric cancer treatment based on network pharmacology and bioinformatics

ZHANG Hao LI Xue-yan LI Ling-min JIAN Bai-yu*

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Abstract

Objective To explore the mechanism of cinobufagin (CBG) in treating gastric cancer based on network pharmacology combined with bioinformatics and molecular docking technology. Methods Active ingredients and potential targets of CBG in treating gastric cancer were collected from PubChem, TCMSP, and SwissTargetPrediction databases. Transcriptional data of gastric cancer samples were obtained from TGGA database, and gastric cancer-related targets were identified through differential gene analysis. Intersection of targets between CBG and gastric cancer diseases was subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Protein-protein interaction (PPI) network of common targets was constructed using STRING database, and core targets were selected using Cytoscape software. Molecular docking verification of core targets screened with SYBYL-X 2.1.1 software was conducted with CBG. Results CBG treatment of gastric cancer involved 59 targets, with 19 key targets identified. Key targets such as aurora kinase A(AURKA), cyclin-dependent kinase 1(CDK1), enhancer of zeste homolog 2(EZH2), hepatocyte growth factor receptor (MET), matrix metallopeptidase 3(MMP-3), progesterone receptor (PGR), prostaglandin-endoperoxide synthase 1(PTGS1), and thymidylate synthase (TYMS) which exhibited good binding activity with CBG and were closely associated with gastric cancer prognosis. Conclusion CBG may exert anti-gastric cancer effects through multiple targets and pathways.

Key words

Cinobufagin / Gastric cancer / TCGA database / Network pharmacology / Molecular docking

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ZHANG Hao LI Xue-yan LI Ling-min JIAN Bai-yu. Investigating mechanism of cinobufagin in gastric cancer treatment based on network pharmacology and bioinformatics[J]. Acta Anatomica Sinica. 2025, 56(1): 43-49 https://doi.org/10.16098/j.issn.0529-1356.2025.01.006

References

［1］Zheng Y, Pan HM. Advances in targeted and immunotherapy for gastric cancer ［J］. Journal of Cancer Research and Prevention, 2024, 51(4): 234-239. (in Chinese)

郑宇,潘宏铭.胃癌靶向及免疫治疗进展［J］.肿瘤防治研究,2024,51(4):234-239.

［2］Wang XF, Zhou P, Tang ZhQ. New advances and development trends in surgical treatment of gastric cancer ［J］. China Journal of Oncology, 2024, 34(3): 250-258. (in Chinese)

汪学非,周鹏,唐兆庆.胃癌外科治疗的新进展及发展趋势［J］.中国癌症杂志,2024,34(3):250-258.

［3］Shi L, Jiao Y, Xue F, et al. Current status of quality research on the traditional chinese medicine chan su ［J］. Pharmaceutical Research, 2024, 43(2): 171-177. (in Chinese)

石丽,焦阳,薛菲,等.中药蟾酥的质量研究现状［J］.药学研究,2024,43(2):171-177.

［4］Liu YY, Sun B, Zhao HY, et al. Metabolic pathways of bufanolides, the active components of bufo gargarizans, based on tissue distribution ［J］. China Journal of Chinese Materia Medica, 2024, 49(4): 932-941. (in Chinese)

刘玉洋,孙博,赵海誉,等.基于组织分布探究中华大蟾蜍功效成分蟾蜍甾烯类体内代谢途径［J］.中国中药杂志,2024,49(4):932-941.

［5］Meng LJ, Kong QH, Jiang N, et al. Chemical constituents and cytotoxic activities of bufo gargarizans skin ［J］. Chinese Traditional Patent Medicine, 2023, 45(11): 362-3626. (in Chinese)

孟令杰,孔庆宏,姜念,等.中华大蟾蜍皮化学成分及其细胞毒活性［J］.中成药,2023,45(11):3622-3626.

［6］Yang HM, Chen T. Research progress on the application of cinobufacini in the treatment of digestive system tumors ［J］. Guangdong Medical Journal, 2014, 35(15): 2453-2455. (in Chinese)

杨宏梅,陈涛.华蟾素在消化系统肿瘤治疗中应用的研究进展［J］.广东医学,2014,35(15):2453-2455.

［7］Xiong X, Lu B, Tian Q, et al. Inhibition of autophagy enhances cinobufagin-induced apoptosis in gastric cancer［J］. Oncol Rep, 2019, 41(1):492-500.

［8］Zhang H, Jian B, Kuang H. Pharmacological effects of cinobufagin［J］. Med Sci Monit. 2023, 29: e940889.

［9］Dai CL, Zhang RJ, An P, et al. Cinobufagin: a promising therapeutic agent for cancer［J］. J Pharm Pharmacol, 2023, 75(9):1141-1153.

［10］Xu XL, Xiao JW, Wei ShJ, et al. Expression of aurora kinase a in gastric cancer tissues and its relationship with clinicopathological characteristics ［J］. Chinese Journal of General Surgery and Clinical Research, 2016, 23(12): 1464-1469. (in Chinese)

徐秀连,肖江卫,魏寿江,等. Aurka在胃癌组织中的表达及其与临床病理学特征关系的研究［J］.中国普外基础与临床杂志,2016,23(12):1464-1469.

［11］Liu Q. Mechanistic study on AURKA regulation of EMT process through histone modification in gastric cancer ［D］. Tianjin:Tianjin Medical University, 2016. (in Chinese)

刘茜.胃癌中AURKA通过组蛋白修饰调节EMT进程的机制研究［D］.天津:天津医科大学,2016.

［12］Do TV, Xiao F, Bickel LE, et al. Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion ［J］. Oncogene, 2014,33(5):539-549.

［13］Tong T, Zhong Y, Kong J, et al. Overexpression of aurora-A contributes to malignant development of human esophageal squamous cell carcinoma［J］. Clinical cancer research: an official journal of the American Association for Cancer Research,2004,10(21):7304-7310.

［14］Jiang KW, Wang Sh, Ye YJ, et al. The expression of cyclin D1 and cyclin-dependent kinase 6 in gastric cancer tissues and their relationship with prognosis ［J］. Chinese Journal of General Surgery, 2005, 20(12): 800-802. (in Chinese)

姜可伟,王杉,叶颖江,等.胃癌组织中细胞周期蛋白D1和细胞周期蛋白质依赖激酶6的表达与预后的关系［J］.中华普通外科杂志,2005,20(12):800-802.

［15］Fu H, Yu AJ, Chen K, et al. Expression of CDC25A and CDK1 in gastric cancer tissues and their clinical significance ［J］. Hebei Medical Journal, 2018, 24(1): 80-83. (in Chinese)

傅华,于爱军,陈凯,等.CDC25A与CDK1在胃癌组织中的表达及其临床意义［J］.河北医学,2018,24(1):80-83.

［16］Yang BY, Chen Q. Advances in research on the correlation between EZH2 gene and gastric cancer ［J］. Journal of Tumor Basic and Clinical Research, 2019, 32(3): 272-276. (in Chinese)

杨宝玉,陈强.EZH2基因与胃癌相关性研究进展［J］.肿瘤基础与临床,2019,32(3):272-276.

［17］Matsukawa Y，Semba S，Kato H．Expression of the enhancer of zeste homolog 2 is correlated with poor prognosis in human gastric cancer［J］．Cancer Sci，2006，97(6): 484-491.

［18］Lu HX, Wei DM, Feng ZhB. Expression and clinical significance of ezh2 in hepatocellular carcinoma ［J］. Acta Anatomica Sinica, 2011, 42(1): 75-79. (in Chinese)

陆海霞,危丹明,冯震博.EZH2在肝细胞癌中的表达及临床意义［J］.解剖学报,2011,42(1):75-79.

［19］Peng Y, Chen HB, Su ZhJ, et al. Expression of EZH2 protein in esophageal cancer tissues ［J］. Acta Anatomica Sinica, 2006, 37(6): 650-655. (in Chinese)

彭燕,陈海滨,苏中静,等.EZH2蛋白在食管癌组织中的表达［J］.解剖学报,2006,37(6):650-655.

［20］Gan L, Xu M, Hua R, et al. The polycomb group protein EZH2 induces epithelial-mesenchymal transition and pluripotent phenotype of gastric cancer cells by binding to PTEN promoter［J］. J Hematol Oncol, 2018, 11(1):9.

［21］Marano L, Chiari R, Fabozzi A, et al. c-Met targeting in advanced gastric cancer: an open challenge［J］. Cancer Lett, 2015, 365(1):30-36.

［22］Janjigian YY, Tang LH, Coit DG, et al. MET expression and amplification in patients with localized gastric cancer［J］. Cancer Epidemiol Biomarkers Prev, 2011, 20(5):1021-1027.

［23］Ge X, Lin F, Wu Z, et al. Role of ROR2 in promoting gastric cancer metastasis by enhancing c-JUN-mediated MMP3 transcription［J］. Ann Transl Med, 2022, 10(20):1117.