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Updated: Nov 24, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Targeting castration-resistant prostate cancer with a novel RORγ antagonist elaiophylin
Jianwei Zheng1, Junfeng Wang2, Qian Wang1
1School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Abstract:
Prostate cancer (PCa) patients who progress to metastatic castration-resistant PCa (mCRPC) mostly have poor outcomes due to the lack of effective therapies. Our recent study established the orphan nuclear receptor RORγ as a novel therapeutic target for CRPC. Here, we reveal that elaiophylin (Elai), an antibiotic from Actinomycete streptomyces, is a novel RORγ antagonist and showed potent antitumor activity against CRPC in vitro and in vivo. We demonstrated that Elai selectively binded to RORγ protein and potently blocked RORγ transcriptional regulation activities. Structure-activity relationship studies showed that Elai occupied the binding pocket with several key interactions. Furthermore, Elai markedly reduced the recruitment of RORγ to its genomic DNA response element (RORE), suppressed the expression of RORγ target genes AR and AR variants, and significantly inhibited PCa cell growth. Importantly, Elai strongly suppressed tumor growth in both cell line based and patient-derived PCa xenograft models. Taken together, these results suggest that Elai is novel therapeutic RORγ inhibitor that can be used as a drug candidate for the treatment of human CRPC.
Insights
Elaiophylin, an antibiotic, acts as a novel RORγ antagonist, demonstrating potent antitumor effects against metastatic castration-resistant prostate cancer (mCRPC) by inhibiting RORγ activity and suppressing tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) presents a significant therapeutic challenge with limited effective treatments.
- The orphan nuclear receptor RORγ has been identified as a promising therapeutic target for CRPC.
Purpose of the Study:
- To investigate elaiophylin (Elai) as a novel RORγ antagonist for CRPC treatment.
- To evaluate the antitumor activity of Elai in vitro and in vivo.
Main Methods:
- Elaiophylin's binding affinity and interaction with RORγ protein were assessed.
- Transcriptional regulation activities of RORγ and its target genes (AR, AR variants) were analyzed.
- Antitumor efficacy of Elai was evaluated in prostate cancer cell lines and xenograft models.
Main Results:
- Elaiophylin selectively binds to RORγ, potently inhibiting its transcriptional activity.
- Elai reduced RORγ recruitment to DNA, suppressed AR and AR variant expression, and inhibited prostate cancer cell growth.
- Elai demonstrated significant tumor growth suppression in both cell line-derived and patient-derived xenograft models.
Conclusions:
- Elaiophylin is a novel RORγ antagonist with potent antitumor activity against CRPC.
- Elai shows potential as a drug candidate for treating human CRPC.
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