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Published on: April 18, 2025
Monotropein attenuates renal cell carcinoma cell progression and M2 macrophage polarization by weakening NF-κB
Heping Qiu1, Fei Liu1, Mei Qiu2
1Department of Urology, The Second Affiliated Hospital of Nanchang University, No.1, Minde Road, East Lake District, Nanchang, 330006, Jiangxi, China.
Purpose:
The study aimed to investigate the effect and mechanism of monotropein on renal cell carcinoma (RCC).
Methods:
After monotropein and NF-κB receptor activator (RANKL) treatment, cell proliferation, invasion, and apoptosis were evaluated using CCK-8, Transwell, and flow cytometry. Primary macrophages co-cultured with monotropein-treated RCC cells were analyzed to evaluate macrophage polarization using qRT-PCR, western blot, and ELISA assays by detecting the expression of M2 markers (CD206, CD168) and cytokines (IL-10, TGF-β). Additionally, the therapeutic efficacy of monotropein was examined using an RCC mouse xenograft model.
Results:
Monotropein could inhibit the proliferation, invasion, and M2 macrophage polarization and accelerate the apoptosis of RCC cells. Mechanistically, monotropein suppressed NF-κB pathway activation in RCC cells and reduced the expression of NF-κB downstream targets, including Bcl-2, c-Myc, and MMP9. RANKL could eliminate the effect of monotropein on RCC progression. In primary macrophages co-cultured with monotropein-treated RCC cells, monotropein downregulated M2 polarization markers and cytokines, further supporting its role in modulating the tumor microenvironment. In mouse models, monotropein reduced RCC tumor growth, induced apoptosis, and blocked NF-κB pathway.
Conclusions:
Monotropein prevents RCC malignant progression and reduces M2 macrophage polarization by suppressing the NF-κB pathway, suggesting that monotropein may serve as a potential therapeutic agent for RCC by targeting both tumor cells and the tumor microenvironment.
Insights
Monotropein inhibits renal cell carcinoma (RCC) progression by reducing cell proliferation and M2 macrophage polarization via the NF-κB pathway. This natural compound shows potential as a therapeutic agent for RCC.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Renal cell carcinoma (RCC) is a significant health concern.
- Understanding the molecular mechanisms and tumor microenvironment interactions is crucial for effective RCC treatment.
- Identifying novel therapeutic agents targeting both cancer cells and their surrounding environment is a key research area.
Purpose of the Study:
- To investigate the therapeutic effects of monotropein on renal cell carcinoma (RCC).
- To elucidate the underlying mechanisms of monotropein's action, particularly its impact on the NF-κB pathway and M2 macrophage polarization.
- To evaluate the potential of monotropein as a novel therapeutic agent for RCC.
Main Methods:
- Cell proliferation, invasion, and apoptosis assays (CCK-8, Transwell, flow cytometry) were performed on RCC cells treated with monotropein.
- Macrophage polarization was assessed in co-culture systems using qRT-PCR, western blot, and ELISA to detect M2 markers and cytokines.
- The therapeutic efficacy of monotropein was evaluated in an RCC mouse xenograft model.
Main Results:
- Monotropein significantly inhibited RCC cell proliferation and invasion while promoting apoptosis.
- Monotropein suppressed NF-κB pathway activation in RCC cells, reducing key downstream targets like Bcl-2, c-Myc, and MMP9.
- Monotropein downregulated M2 macrophage polarization markers and cytokines, indicating modulation of the tumor microenvironment. RANKL reversed these effects.
- In vivo studies confirmed that monotropein reduced tumor growth, induced apoptosis, and inhibited the NF-κB pathway in an RCC mouse model.
Conclusions:
- Monotropein effectively prevents malignant progression of RCC.
- Monotropein exerts its anti-cancer effects by suppressing the NF-κB pathway and reducing M2 macrophage polarization.
- Monotropein demonstrates potential as a therapeutic agent for RCC, targeting both tumor cells and the tumor microenvironment.
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