Dataset Information

Diptoindonesin G antagonizes AR signaling and enhances the efficacy of antiandrogen therapy in prostate cancer.

ABSTRACT:

Background

The androgen receptor (AR) signaling pathway has been well demonstrated to play a crucial role in the development, progression, and drug resistance of prostate cancer. Although the current anti-androgen therapy could significantly benefit prostate cancer patients initially, the efficacy of the single drug usually lasts for a relatively short period, as drug resistance quickly emerges.

Methods

We have performed an unbiased bioinformatics analysis using the RNA-seq results in 22Rv1 cells to identify the cell response toward Dip G treatment. The RNA-seq results were validated by qRT-PCR. Protein levels were detected by western blot or staining. Cell viability was measured by Aquabluer and colony formation assay.

Results

Here, we identified that Diptoindonesin G (Dip G), a natural extracted compound, could promote the proteasome degradation of AR and polo-like kinase 1 (PLK1) through modulating the activation of CHIP E3 ligase. Administration of Dip G has shown a profound efficiency in the suppression of AR and PLK1, not only in androgen-dependent LNCaP cells but also in castration-resistant and enzalutamide-resistant cells in a CHIP-dependent manner. Through co-targeting the AR signaling, Dip G robustly improved the efficacy of HSP90 inhibitors and enzalutamide in both human prostate cancer cells and in vivo xenograft mouse model.

Conclusions

Our results revealed that Dip G-mediated AR degradation would be a promising and valuable therapeutic strategy in the clinic.

SUBMITTER: Mao F

PROVIDER: S-EPMC9035130 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Diptoindonesin G antagonizes AR signaling and enhances the efficacy of antiandrogen therapy in prostate cancer.

Mao Fengyi F Kong Yifan Y Liu Jinghui J Rao Xiongjian X Li Chaohao C Donahue Kristine K Zhang Yanquan Y Jones Katelyn K Zhang Qiongsi Q Xu Wei W Liu Xiaoqi X

The Prostate 20220324 8

<h4>Background</h4>The androgen receptor (AR) signaling pathway has been well demonstrated to play a crucial role in the development, progression, and drug resistance of prostate cancer. Although the current anti-androgen therapy could significantly benefit prostate cancer patients initially, the efficacy of the single drug usually lasts for a relatively short period, as drug resistance quickly emerges.<h4>Methods</h4>We have performed an unbiased bioinformatics analysis using the RNA-seq result ...[more]

PMID: 35322879

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Project description:BackgroundSalvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown.MethodsIn a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival.ResultsThe median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P=0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P=0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001).ConclusionsThe addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo. (Funded by the National Cancer Institute and AstraZeneca; RTOG 9601 ClinicalTrials.gov number, NCT00002874 .).

Dataset Information

Diptoindonesin G antagonizes AR signaling and enhances the efficacy of antiandrogen therapy in prostate cancer.

Background

Methods

Results

Conclusions

Publications

Diptoindonesin G antagonizes AR signaling and enhances the efficacy of antiandrogen therapy in prostate cancer.

Similar Datasets

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