Abstract
Purpose
Glioblastoma is one of the malignant tumors with poor prognosis and no effective treatment is available at present.
Methods
To study the effect of cordycepin combined with temozolomide on glioblastoma, we explored the effect of the combination based on network pharmacology and biological verification.
Results
It was found that the drug combination significantly inhibited the cell growth, proliferation, migration and invasion of LN-229 cells. Drug combination inhibited epithelial–mesenchymal transition (EMT) by up-regulating the expression of E-cadherin and suppressing the expression of N-cadherin, Zeb1 and Twist1. Through network pharmacology, we further explored the molecular mechanism of drug combination against glioblastoma, and 36 drug-disease common targets were screened. The GO biological process analysis included 44 items (P < 0.01), which mainly involved the regulation of apoptosis, cell proliferation, cell migration, etc. The enrichment analysis of KEGG pathways included 28 pathways (P < 0.05), and the first four pathways were "MicroRNA in cancer, Proteoglycans in cancer, Pathways in cancer and PI3K-AKT signaling pathway". We detected the expression of important genes in the pathways and PPI network, and the results showed that the drug combination down-regulated NFKB1, MYC, MMP-9, MCL1, CTNNB1, and up-regulated PDCD4.
Conclusion
Cordycepin combined with temozolomide may down-regulate MYC through “MicroRNA in cancer, Proteoglycans in cancer, Pathways in cancer and PI3K-AKT signaling pathway”, which in turn regulate the expression of MCL1, CTNNB1, MMP9, PDCD4, thus regulating cell proliferation, migration and apoptosis in glioblastoma.
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Availability of data and materials
All data generated or analyzed in the course of this study are available upon request. The corresponding author can be contacted to obtain the data, and the email address is jingchen1121@163.com.
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Funding
The study has been supported by the Key Discipline Construction Project of the Union Hospital of Fujian Province, China, No. 211002. And supported by the Natural Science Foundation of Fujian Province of China, No. 2021J01781.
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All authors contributed to study conception and design. Material preparation, data collection and analysis were performed by S-XZ, JC, B-BZ, QZ, S-SS and G-LZ. The research was developed and designed by JC, S-XZ and B-BZ, who also carried out and analyzed the experiments and wrote the manuscript; technical support was supplied by QZ, G-LZ and S-SS, who also performed part of the experiments and processed the results. S-XZ and JC contributed equally to the work. The final version of the text was reviewed and approved by all authors.
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The authors declare that they have no known competing financial interests in this work. Shi-Xing Zheng, Jing Chen, Bing-Bo Zhuang, Qiang Zhang, Song-Sheng Shi and Guo-Liang Zhang declare that they have no financial interests.
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Zheng, SX., Chen, J., Zhuang, BB. et al. Cordycepin improves sensitivity to temozolomide in glioblastoma cells by down-regulating MYC. J Cancer Res Clin Oncol 149, 16055–16067 (2023). https://doi.org/10.1007/s00432-023-05347-0
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DOI: https://doi.org/10.1007/s00432-023-05347-0