Skip to content
2000
image of Exploring Compound Kushen Injection’s Anticancer Properties in Hepatocellular Carcinoma: An Integrated Approach of Network Pharmacology, Bioinformatics, and Experimental Validation

Abstract

Background

Hepatocellular carcinoma (HCC), commonly referred to as primary liver cancer, is a malignant neoplasm that originates within the liver. Conventional treatment modalities frequently result in less than satisfactory outcomes, primarily attributed to the intricate physiological and pathological contexts. Compound Kushen Injection (CKI), formulated from the botanicals and , is employed as a supplementary therapy in the treatment of advanced-stage malignant tumors, including HCC.

Objective

Our study combined network pharmacology, bioinformatics, GeneMANIA-based functional association (GMFA), and experimental validation to elucidate CKI's therapeutic targets and mechanisms.

Methods

STRING was used to build a protein-protein interaction network, and GO and KEGG analyses were performed with DAVID and ShinyGO on the overlapping targets of CKI and HCC. Hub targets were identified using CytoHubba and their clinical relevance was confirmed with GEPIA2. GMFA and TIMER assessed the functions of key hub genes. The findings were further verified through significant KEGG analysis, molecular docking, and experimental validation.

Results

10 hub targets were identified for CKI against HCC and analyzed for their impact on HCC patient survival and gene expression. GMFA confirmed four key hub genes, and TIMER assessed the correlation between SRC expression and immune infiltration. Significant KEGG analysis highlighted SRC's role in cell proliferation and migration through the MMP/EGFR-PI3K/AKT pathway. Molecular docking showed interactions between SRC and desmethylanhydroicaritin or resokaempferol. Experiments in HepG2 cells confirmed CKI's inhibitory effect on tumor cells.

Conclusion

CKI’s anti-HCC effects may be exerted by regulating SRC active compounds desmethylanhydroicaritin and resokaempferol.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdrr/10.2174/0125899775387801250722064737
2025-08-06
2025-10-19

  • From This Site

    /content/journals/cdrr/10.2174/0125899775387801250722064737
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Sperandio R.C. Pestana R.C. Miyamura B.V. Kaseb A.O. Hepatocellular carcinoma immunotherapy. Annu. Rev. Med. 2022 73 1 267 278 10.1146/annurev‑med‑042220‑021121 34606324
    [Google Scholar]
  2. Ganesan P. Kulik L.M. Hepatocellular carcinoma: New developments. Clin. Liver Dis. 2023 27 1 85 102 10.1016/j.cld.2022.08.004 36400469
    [Google Scholar]
  3. Chakraborty E. Sarkar D. Emerging therapies for hepatocellular carcinoma (HCC). Cancers 2022 14 11 2798 10.3390/cancers14112798 35681776
    [Google Scholar]
  4. Yang J.D. Hainaut P. Gores G.J. Amadou A. Plymoth A. Roberts L.R. A global view of hepatocellular carcinoma: Trends, risk, prevention and management. Nat. Rev. Gastroenterol. Hepatol. 2019 16 10 589 604 10.1038/s41575‑019‑0186‑y 31439937
    [Google Scholar]
  5. Gilles H. Garbutt T. Landrum J. Hepatocellular Carcinoma. Crit. Care Nurs. Clin. North Am. 2022 34 3 289 301 10.1016/j.cnc.2022.04.004 36049848
    [Google Scholar]
  6. Fan Q.Q. She G.M. Wei J. Evaluation and mechanism of antitumor and analgesic activity of compound matrine injection. Zhongguo Zhongyao Zazhi 2022 47 2712 2720 10.19540/j.cnki.cjcmm.20211129.701 35718491
    [Google Scholar]
  7. Hao C.H. Tian L.B. He J. Preventive effect and survival function analysis of compound matrine injection on postoperative recurrence in patients with primary liver cancer. Chin J Integr Trad West Med Liver Dis 2020 30 303 306 10.3969/j.issn.1001‑1528.2018.01.055
    [Google Scholar]
  8. Li C. Niu D. Zhu R. Adjunctive effect of compound Kushen injection for cancer: An overview of systematic reviews. J. Ethnopharmacol. 2023 317 116778 10.1016/j.jep.2023.116778 37328082
    [Google Scholar]
  9. Zhu J.B. Improvement of therapeutic effect, liver function and side effects of compound matrine injection combined with TACE in patients with advanced liver cancer. Pract Clin J Integr Trad Chin West Med 2020 20 95 96 10.13638/j.issn.1671‑4040.2020.05.048
    [Google Scholar]
  10. Yang Y. Sun M. Yao W. Compound kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib. J. Immunother. Cancer 2020 8 1 000317 10.1136/jitc‑2019‑000317 32179631
    [Google Scholar]
  11. Joshi C.P. Baldi A. Kumar N. Pradhan J. Harnessing network pharmacology in drug discovery: An integrated approach. Naunyn Schmiedebergs Arch. Pharmacol. 2024 ••• 10.1007/s00210‑024‑03625‑3 39621088
    [Google Scholar]
  12. Ding J. Tang S. Mei Z. Vina-GPU 2.0: Further accelerating autodock vina and its derivatives with graphics processing units. J. Chem. Inf. Model. 2023 63 7 1982 1998 10.1021/acs.jcim.2c01504 36941232
    [Google Scholar]
  13. Franz M. Rodriguez H. Lopes C. GeneMANIA update 2018. Nucleic Acids Res. 2018 46 W1 W60-4 10.1093/nar/gky311 29912392
    [Google Scholar]
  14. Li T. Fu J. Zeng Z. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020 48 W1 W509-14 10.1093/nar/gkaa407 32442275
    [Google Scholar]
  15. Tang Z. Kang B. Li C. Chen T. Zhang Z. GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019 47 W1 W556-60 10.1093/nar/gkz430 31114875
    [Google Scholar]
  16. Kim S. Chen J. Cheng T. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res. 2021 49 D1 D1388 D1395 10.1093/nar/gkaa971 33151290
    [Google Scholar]
  17. Daina A. Michielin O. Zoete V. SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019 47 W1 W357-64 10.1093/nar/gkz382 31106366
    [Google Scholar]
  18. Barshir R. Fishilevich S. Iny-Stein T. GeneCaRNA: A comprehensive gene-centric database of human non-coding RNAs in the GeneCards suite. J. Mol. Biol. 2021 433 11 166913 10.1016/j.jmb.2021.166913 33676929
    [Google Scholar]
  19. Szklarczyk D. Gable A.L. Nastou K.C. The STRING database in 2021: Customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2021 49 D1 D605 D612 10.1093/nar/gkaa1074 33237311
    [Google Scholar]
  20. Franz M. Lopes C.T. Fong D. Cytoscape.js 2023 update: A graph theory library for visualization and analysis. Bioinformatics 2023 39 1 btad031 10.1093/bioinformatics/btad031 36645249
    [Google Scholar]
  21. Sherman B.T. Hao M. Qiu J. DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022 50 W1 W216-21 10.1093/nar/gkac194 35325185
    [Google Scholar]
  22. Tang D. Chen M. Huang X. SRplot: A free online platform for data visualization and graphing. PLoS One 2023 18 11 0294236 10.1371/journal.pone.0294236 37943830
    [Google Scholar]
  23. Ge S.X. Jung D. Yao R. Shiny G.O. A graphical gene-set enrichment tool for animals and plants. Bioinformatics 2020 36 8 2628 2629 10.1093/bioinformatics/btz931 31882993
    [Google Scholar]
  24. Burley S.K. Bhikadiya C. Bi C. RCSB Protein Data Bank (RCSB.org): Delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning. Nucleic Acids Res. 2023 51 D1 D488 D508 10.1093/nar/gkac1077 36420884
    [Google Scholar]
  25. Hasan T.N. Naqvi S.S. Rehman M.U. Ginger ring compounds as an inhibitor of spike binding protein of alpha, beta, gamma and delta variants of SARS-CoV-2: An in-silico study. Narra J 2023 3 1 98 10.52225/narra.v3i1.98 38455706
    [Google Scholar]
  26. Rosignoli S. Paiardini A. Boosting the full potential of PyMOL with structural biology plugins. Biomolecules 2022 12 12 1764 10.3390/biom12121764 36551192
    [Google Scholar]
  27. Chen Y. Yang Y. Wang N. β‐Sitosterol suppresses hepatocellular carcinoma growth and metastasis via FOXM1‐regulated Wnt/β‐catenin pathway. J. Cell. Mol. Med. 2024 28 3 18072 10.1111/jcmm.18072 38063438
    [Google Scholar]
  28. Zhang L.H. Zhang W.Y. Xiong J.M. Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation. Chin. J. Nat. Med. 2022 20 1 43 53 10.1016/S1875‑5364(22)60144‑4 35101249
    [Google Scholar]
  29. Gautheron G. Péraldi-Roux S. Vaillé J. The flavonoid resokaempferol improves insulin secretion from healthy and dysfunctional pancreatic β ‐cells. Br. J. Pharmacol. 2025 182 1 52 68 10.1111/bph.17304 39327688
    [Google Scholar]
  30. Kang C.W. Kim N.H. Jung H.A. Desmethylanhydroicaritin isolated from Sophora flavescens, shows antitumor activities in U87MG cells via inhibiting the proliferation, migration and invasion. Environ. Toxicol. Pharmacol. 2016 43 140 148 10.1016/j.etap.2016.03.003 26991848
    [Google Scholar]
  31. Zhang W. Cao X. Wu H. Zhong X. Shi Y. Sun Z. Function of steroid receptor coactivators in T cells and cancers: Implications for cancer immunotherapy. Crit. Rev. Immunol. 2024 44 6 111 126 10.1615/CritRevImmunol.2024051613 38848298
    [Google Scholar]
  32. Chang C.W. Chin Y.H. Liu M.S. Shen Y.C. Yan S.J. High sugar diet promotes tumor progression paradoxically through aberrant upregulation of pepck1. Cell. Mol. Life Sci. 2024 81 1 396 10.1007/s00018‑024‑05438‑2 39261338
    [Google Scholar]
  33. Wang X. Wang B. Li F. The c‐Src/LIST positive feedback loop sustains tumor progression and chemoresistance. Adv. Sci. 2023 10 20 2300115 10.1002/advs.202300115 37156751
    [Google Scholar]
/content/journals/cdrr/10.2174/0125899775387801250722064737
Loading
Exploring Compound Kushen Injection’s Anticancer Properties in Hepatocellular Carcinoma: An Integrated Approach of Network Pharmacology, Bioinformatics, and Experimental Validation
Bentham Science Publishers ; https://doi.org/10.2174/0125899775387801250722064737
/content/journals/cdrr/10.2174/0125899775387801250722064737
/content/journals/cdrr/10.2174/0125899775387801250722064737
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: hepatocellular carcinoma ; HepG2 cells ; Compound Kushen Injection ; GMFA ; bioinformatics ; network pharmacology

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test