The BRD4 inhibitor JQ1 suppresses tumor growth by reducing c-Myc expression in endometrial cancer
Yingxin Pang1,2,3, Gaigai Bai1,2,3, Jing Zhao1
1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, No.107 Wenhua West Road, Jinan, 250012, Shandong, China.
Background:
Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Efficacy of the bromodomain 4 (BRD4) inhibitor JQ1 has been reported for the treatment of various human cancers, but its potential impact on EC remains unclear. We therefore aimed to elucidate the function of BRD4 and the effects of JQ1 in EC in vivo and in vitro.
Methods:
The mRNA expression of BRD4 was evaluated using datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). BRD4 protein expression in EC tissues was measured using immunohistochemistry (IHC) assays. The effects of JQ1 on EC were determined by using MTT and colony formation assays, flow cytometry and xenograft mouse models. The underlying mechanism was also examined by western blot and small interfering RNA (siRNA) transfection.
Results:
BRD4 was overexpressed in EC tissues, and the level of BRD4 expression was strongly related to poor prognosis. The BRD4-specific inhibitor JQ1 suppressed cell proliferation and colony formation and triggered cell apoptosis, cell cycle arrest, and changes in the expression of proteins in related signaling pathways. Moreover, JQ1 decreased the protein expression of BRD4 and c-Myc, and knockdown of BRD4 or c-Myc reduced the viability of EC cells. Intraperitoneal administration of JQ1 (50 mg/kg) significantly suppressed the tumorigenicity of EC cells in a xenograft mouse model.
Conclusion:
Our results demonstrate that BRD4 is a potential marker of EC and that the BRD4 inhibitor JQ1 is a promising chemotherapeutic agent for the treatment of EC.
Insights
Bromodomain 4 (BRD4) is overexpressed in endometrial cancer (EC), correlating with poor prognosis. The BRD4 inhibitor JQ1 effectively suppressed EC growth in vitro and in vivo, indicating its potential as a therapeutic agent.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Endometrial cancer (EC) is a prevalent gynecological malignancy.
- The therapeutic potential of bromodomain 4 (BRD4) inhibitor JQ1 in EC is not well-established.
Purpose of the Study:
- To investigate the role of BRD4 in EC.
- To evaluate the efficacy of JQ1 as a treatment for EC.
Main Methods:
- BRD4 mRNA and protein expression analysis in EC tissues.
- In vitro assays (MTT, colony formation, flow cytometry) to assess JQ1 effects.
- In vivo xenograft mouse models to evaluate JQ1's anti-tumor activity.
- Western blot and siRNA for mechanistic studies.
Main Results:
- BRD4 was overexpressed in EC tissues and linked to poor prognosis.
- JQ1 inhibited EC cell proliferation, colony formation, and induced apoptosis and cell cycle arrest.
- JQ1 reduced BRD4 and c-Myc protein levels; BRD4 or c-Myc knockdown decreased EC cell viability.
- JQ1 significantly suppressed tumor growth in a xenograft mouse model.
Conclusions:
- BRD4 is a potential biomarker for EC.
- JQ1 demonstrates promise as a chemotherapeutic agent for endometrial cancer treatment.
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