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.

Abstract

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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