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Updated: Aug 28, 2025

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Cordycepin Inhibits Growth and Metastasis Formation of MDA-MB-231 Xenografts in Nude Mice by Modulating the Hedgehog
Wenya Wu1,2, Xiaomin Li1,2, Meng Qi1,2
1College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
Abstract:
We previously found that cordycepin inhibits the growth and metastasis formation of MDA-MB-231 cells through the Hedgehog pathway but has not validated this in vivo. In this study, we confirmed cordycepin's anti-triple-negative breast cancer (TNBC) effect in nude mice and documented its mechanism. We found that cordycepin reduced the volume and weight of MDA-MB-231 xenografts and affected the expression of proliferation-, apoptosis-, epithelial-mesenchymal transition-, and matrix metalloproteinase-related proteins without side effects. RNA sequencing screening, pathway enrichment, and the protein network interaction analysis revealed enriched pathways and targets mainly concentrated on the Hedgehog pathway and its core components of SHH and GLI2. This indicates that the Hedgehog pathway plays a central role in the cordycepin-mediated regulation of growth and metastasis formation in TNBC. The database analysis of the Hedgehog pathway markers (SHH, PTCH1, SMO, GLI1, and GLI2) revealed that the Hedgehog pathway is activated in breast cancer tissues, and its high expression is not conducive to a patient's survival. Finally, we verified that cordycepin effectively inhibited the Hedgehog pathway in TNBC through Western blotting and immunohistochemistry. This study found that cordycepin could regulate the growth and metastasis formation of TNBC through the Hedgehog pathway in vivo, which provides new insights for targeting and treating breast cancer.
Insights
Cordycepin effectively inhibits triple-negative breast cancer (TNBC) growth and metastasis in vivo by targeting the Hedgehog pathway. This study validates cordycepin
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cordycepin previously showed in vitro inhibition of MDA-MB-231 cell growth and metastasis via the Hedgehog pathway.
- Validation of cordycepin's in vivo efficacy and mechanism against triple-negative breast cancer (TNBC) was lacking.
Purpose of the Study:
- To confirm cordycepin's anti-TNBC effects in vivo.
- To elucidate the mechanism of cordycepin's action in TNBC, focusing on the Hedgehog pathway.
Main Methods:
- In vivo xenograft models using MDA-MB-231 cells in nude mice.
- RNA sequencing, pathway enrichment, and protein network analysis.
- Western blotting and immunohistochemistry to validate pathway inhibition.
Main Results:
- Cordycepin significantly reduced xenograft volume and weight with no observed side effects.
- Hedgehog pathway components (SHH, GLI2) were identified as key targets.
- Hedgehog pathway activation correlates with poor survival in breast cancer patients.
Conclusions:
- Cordycepin demonstrates in vivo efficacy against TNBC by inhibiting the Hedgehog pathway.
- Targeting the Hedgehog pathway with cordycepin offers a potential therapeutic strategy for TNBC.
- This study provides novel insights into cordycepin's mechanism for treating breast cancer.
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