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Published on: March 28, 2021
Cordycepin improves sensitivity to temozolomide in glioblastoma cells by down-regulating MYC
Shi-Xing Zheng1, Jing Chen2, Bing-Bo Zhuang1
1Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou, 350001, Fujian, China.
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.
Insights
This study shows cordycepin and temozolomide combination effectively inhibits glioblastoma growth and migration. The combination targets key cancer pathways, offering a potential new treatment for this aggressive brain tumor.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Glioblastoma is an aggressive brain tumor with limited treatment options and poor prognosis.
- Current treatments for glioblastoma often face challenges with efficacy and resistance.
Purpose of the Study:
- To investigate the synergistic effects of cordycepin combined with temozolomide on glioblastoma.
- To elucidate the molecular mechanisms underlying the anti-cancer activity of this drug combination using network pharmacology and biological validation.
Main Methods:
- Network pharmacology was employed to identify potential drug targets and pathways.
- In vitro studies using LN-229 glioblastoma cells were conducted to assess cell growth, proliferation, migration, and invasion.
- Gene and protein expression levels of key molecules involved in cancer pathways were analyzed.
Main Results:
- The combination of cordycepin and temozolomide significantly inhibited glioblastoma cell growth, proliferation, migration, and invasion.
- The drug combination suppressed epithelial-mesenchymal transition (EMT) by modulating E-cadherin, N-cadherin, Zeb1, and Twist1 expression.
- Network pharmacology identified 36 common targets and highlighted pathways such as "MicroRNA in cancer" and "PI3K-AKT signaling pathway"; key gene expression changes included down-regulation of MYC and up-regulation of PDCD4.
Conclusions:
- Cordycepin and temozolomide combination demonstrates significant anti-glioblastoma activity.
- The mechanism involves down-regulating MYC via specific cancer-related pathways, subsequently affecting cell proliferation, migration, and apoptosis.
- This combination therapy presents a promising strategy for glioblastoma treatment.
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