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Updated: Dec 31, 2025
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Expression profile-based screening for critical genes reveals S100A4, ACKR3 and CDH1 in docetaxel-resistant prostate
Sha Zhu1,2, Zhixue Min3, Xianli Qiao2
1Key laboratory of Tumor Immunology, Center of Infection and Immunization, Department of Immunology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, P. R. China.
Abstract:
Docetaxel is a first-line anticancer drug widely used in the treatment of advanced prostate cancer. However, its therapeutic efficacy is limited by its side effects and the development of chemoresistance by the tumor. Using a gene differential expression microarray, we identified 449 genes differentially expressed in docetaxel-resistant DU145 and PC3 cell lines as compared to docetaxel-sensitive controls. Moreover, western blotting and immunohistochemistry revealed altered expression of S100A4, ACKR3 and CDH1in clinical tumor samples. Cytoscape software was used to investigate the relationship between critical proteins and their signaling transduction networks. Functional and pathway enrichment analyses revealed that these signaling pathways were closely related to cellular proliferation, cell adhesion, cell migration and metastasis. In addition, ACKR3 knockout using the crispr/cas9 method andS100A4knockdownusing targeted shRNA exerted additive effects suppressing cancer cell proliferation and migration. This exploratory analysis provides information about potential candidate genes. It also provides new insight into the molecular mechanism underlying docetaxel-resistance in androgen-independent prostate cancer and highlights potential targets to improve therapeutic outcomes.
Insights
This study identifies 449 differentially expressed genes in docetaxel-resistant prostate cancer cells, revealing key proteins like S100A4 and ACKR3 involved in chemoresistance and metastasis. Targeting these genes may improve treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Docetaxel is a primary treatment for advanced prostate cancer.
- Therapeutic success is hindered by side effects and chemoresistance.
- Understanding resistance mechanisms is crucial for improving patient outcomes.
Purpose of the Study:
- To identify genes and pathways involved in docetaxel resistance in prostate cancer.
- To explore potential therapeutic targets for overcoming chemoresistance.
Main Methods:
- Gene differential expression microarray analysis of docetaxel-resistant and sensitive cell lines.
- Western blotting and immunohistochemistry on clinical samples.
- CRISPR/Cas9 and shRNA for gene manipulation (ACKR3 and S100A4).
- Bioinformatic analysis using Cytoscape for pathway and network investigation.
Main Results:
- Identified 449 differentially expressed genes in resistant cells.
- Confirmed altered expression of S100A4, ACKR3, and CDH1 in clinical samples.
- Signaling pathways related to proliferation, adhesion, migration, and metastasis were implicated.
- ACKR3 knockout and S100A4 knockdown showed additive effects in suppressing cancer cell growth and migration.
Conclusions:
- S100A4, ACKR3, and CDH1 are potential biomarkers and therapeutic targets for docetaxel-resistant prostate cancer.
- The study provides insights into the molecular mechanisms of chemoresistance.
- Targeting identified pathways and genes may enhance therapeutic efficacy in prostate cancer treatment.
