Related Experiment Video
Updated: May 24, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Role of dutasteride in pre-clinical ETS fusion-positive prostate cancer models
Bushra Ateeq1, Adaikkalam Vellaichamy, Scott A Tomlins
1Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Background:
Androgens play a crucial role in prostate cancer, hence the androgenic pathway has become an important target of therapeutic intervention. Previously we discovered that gene fusions between the 5'-untranslated region of androgen regulated gene TMPRSS2 and the ETS transcription factor family members were present in a majority of the prostate cancer cases. The resulting aberrant overexpression of ETS genes drives tumor progression.
Methods:
Here, we evaluated the expression levels of 5α-reductase isoenzymes in prostate cancer cell lines and tissues. We tested the effect of dutasteride, a 5α-reductase inhibitor, in TMPRSS2-ERG fusion-positive VCaP cell proliferation and cell invasion. We also evaluated the effect of dutasteride on the TMPRSS2-ERG fusion gene expression. Finally, we tested dutasteride alone or in combination with an anti-androgen in VCaP cell xenografts tumor model.
Results:
Our data showed that 5α-reductase SRD5A1 and SRD5A3 isoenzymes that are responsible for the conversion of testosterone to DHT, are highly expressed in metastatic prostate cancer compared to benign and localized prostate cancer. Dutasteride treatment attenuated VCaP cell proliferation and invasion. VCaP cells pre-treated with dutasteride showed a reduction in ERG and PSA expression. In vivo studies demonstrated that dutasteride in combination with the anti-androgen bicalutamide significantly decreased tumor burden in VCaP cell xenograft model.
Conclusions:
Our findings suggest that dutasteride can inhibit ERG fusion-positive cell growth and in combination with anti-androgen, significantly reduce the tumor burden. Our study suggests that anti-androgens used in combination with dutasteride could synergistically augment the therapeutic efficacy in the treatment of ETS-positive prostate cancer.
Insights
Dutasteride inhibits prostate cancer cell growth and invasion by targeting 5α-reductase. Combining dutasteride with anti-androgens significantly reduces tumor burden in ETS-positive prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Androgens are critical in prostate cancer, making the androgenic pathway a key therapeutic target.
- TMPRSS2-ERG gene fusions lead to overexpression of ETS genes, driving prostate cancer progression.
- 5α-reductase isoenzymes (SRD5A1 and SRD5A3) are highly expressed in metastatic prostate cancer.
Purpose of the Study:
- To evaluate the role of 5α-reductase isoenzymes in prostate cancer.
- To assess the efficacy of dutasteride, a 5α-reductase inhibitor, in TMPRSS2-ERG fusion-positive prostate cancer models.
- To investigate the synergistic effect of dutasteride and anti-androgens in prostate cancer treatment.
Main Methods:
- Assessed 5α-reductase isoenzyme expression in prostate cancer cell lines and tissues.
- Tested dutasteride's effect on VCaP cell proliferation, invasion, and TMPRSS2-ERG gene expression.
- Evaluated dutasteride alone and in combination with bicalutamide in a VCaP cell xenograft model.
Main Results:
- SRD5A1 and SRD5A3 were highly expressed in metastatic prostate cancer.
- Dutasteride reduced VCaP cell proliferation and invasion, and decreased ERG and PSA expression.
- Dutasteride combined with bicalutamide significantly reduced tumor burden in vivo.
Conclusions:
- Dutasteride inhibits growth and invasion of ERG fusion-positive prostate cancer cells.
- Combination therapy with dutasteride and anti-androgens shows synergistic efficacy.
- This combination could enhance therapeutic outcomes for ETS-positive prostate cancer.
