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Updated: Nov 22, 2025
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Mesenchymal stem cells desensitize castration-resistant prostate cancer to docetaxel chemotherapy via inducing
Yang Yu1, Fu-Han Yang1, Wen-Tao Zhang1
1Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Background:
Mesenchymal stem cells (MSCs) have been proved to drive castration resistant prostate cancer (CRPC). In this study, we aim to investigate the contribution of MSCs to the development of docetaxel resistance in CRPC cells and its potential mechanisms.
Methods:
The effect of MSCs on CRPC cells resistance to docetaxel was determined using in vivo and in vitro approaches. CCK8 and PI/Annexin V-FITC assay were used to examined the cell viability and apoptosis. The concentration of transforming growth factor-β1 was measured by enzyme-linked immunosorbent assay and small interfering RNA was used for functional analyses.
Results:
MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion in vivo and in vitro. CRPC cells cocultured with MSCs under docetaxel administration have an increased autophagy activation, while autophagy inhibitor could effectively reversed MSCs-induced resistance to docetaxel. Additionally, MSCs-induced CRPC cell autophagy increase under docetaxel administration depends on MSCs secreting TGF-β1 and inhibition of TGF-β1 secretion in MSCs could consequently increase the sensitivity of CRPC cells to docetaxel.
Conclusions:
These results suggest that docetaxel administrated CRPC cells may elicit MSCs secreting TGF-β1 increase, which desensitizes CRPC to docetaxel chemotherapy accelerating chemoresistance occurrence via inducing cell autophagy.
Insights
Mesenchymal stem cells (MSCs) promote docetaxel resistance in castration-resistant prostate cancer (CRPC) by increasing cell autophagy. This resistance is mediated by MSCs secreting TGF-β1, highlighting a potential therapeutic target for CRPC treatment.
Area of Science:
- Oncology
- Cancer Biology
- Stem Cell Research
Background:
- Mesenchymal stem cells (MSCs) are known to promote castration-resistant prostate cancer (CRPC) progression.
- Understanding the role of MSCs in chemoresistance is crucial for effective CRPC treatment.
Purpose of the Study:
- To investigate how MSCs contribute to docetaxel resistance in CRPC cells.
- To elucidate the underlying mechanisms of MSC-mediated chemoresistance.
Main Methods:
- In vivo and in vitro models were used to assess MSCs' effect on CRPC cells.
- Cell viability and apoptosis were measured using CCK8 and PI/Annexin V-FITC assays.
- Transforming growth factor-β1 (TGF-β1) levels were quantified, and its role was investigated using small interfering RNA (siRNA).
Main Results:
- MSCs significantly reduced CRPC cell sensitivity to docetaxel, inhibiting proliferation and apoptosis.
- Co-culture with MSCs under docetaxel treatment increased autophagy in CRPC cells.
- Inhibition of autophagy reversed MSC-induced docetaxel resistance.
- MSCs' secretion of TGF-β1 was identified as the key mediator of increased autophagy and docetaxel resistance.
Conclusions:
- MSCs promote docetaxel resistance in CRPC by secreting TGF-β1, which induces autophagy.
- This mechanism accelerates chemoresistance, suggesting TGF-β1 and autophagy as potential therapeutic targets.
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