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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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Ezetimibe mediated RPS6KA2 inhibits colorectal cancer proliferation via PCSK9/MAPK signaling pathway

Yu Wang1, Yuting Wang1, Huabin Gao1

  • 1Department of Pathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.

Cancer Treatment and Research Communications
|March 20, 2025
PubMed

Insights

Ezetimibe inhibits colorectal cancer (CRC) progression by increasing RPS6KA2 and decreasing PCSK9/MAPK signaling. This discovery offers a new therapeutic strategy for treating CRC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Colorectal cancer (CRC) remains a significant health challenge.
  • Understanding the molecular mechanisms underlying CRC progression is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the anti-cancer effects and molecular mechanisms of ezetimibe in colorectal cancer.
  • To identify potential molecular targets of ezetimibe in CRC.

Main Methods:

  • In vitro cell culture experiments using CRC cell lines.
  • In vivo studies in animal models.
  • Analysis of human CRC tissue samples.
  • Western blotting and gene expression analysis.

Main Results:

  • Ezetimibe significantly inhibited CRC proliferation and progression.
  • RPS6KA2 was identified as a key target gene, with its expression downregulated in CRC tissues and inversely correlated with tumor stage and invasion.
  • RPS6KA2 suppressed CRC cell proliferation, migration, and invasion by downregulating PCSK9 and the MAPK signaling pathway.
  • PCSK9 expression was upregulated in CRC and associated with advanced tumor classification and stage, promoting CRC cell growth and metastasis.

Conclusions:

  • Ezetimibe exerts anti-CRC effects by upregulating RPS6KA2 and downregulating the PCSK9/MAPK signaling pathway.
  • RPS6KA2 and PCSK9 represent potential therapeutic targets for CRC intervention.
  • This study provides novel insights into the molecular basis of ezetimibe's action in CRC.
Keywords:
Colorectal cancerEzetimibeMAPKPCSK9RPS6KA2

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