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CSF2 promotes chemoresistance in colorectal cancer by regulating Notch pathway

Hairong Zhou1, Zhenyuan Gao1, Xiao Wu1

  • 1Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical University, No.287 Changhuai Road, Bengbu, 233004, Anhui, China.

Discover Oncology
|April 9, 2025
PubMed
Abstract

Insights

Colorectal cancer resistance to chemotherapy drugs like 5-fluorouracil (5FU) and oxaliplatin (OXP) is linked to poor outcomes. This study found that colony-stimulating factor 2 (CSF2) silencing inhibits this drug resistance by regulating the Notch signaling pathway.

Area of Science:

  • Oncology
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) drug resistance to 5-fluorouracil (5FU) and oxaliplatin (OXP) correlates with poor patient prognosis.
  • Colony-stimulating factor 2 (CSF2) is investigated for its role in mediating CRC chemoresistance.

Purpose of the Study:

  • To investigate the effect of colony-stimulating factor 2 (CSF2) on colorectal cancer (CRC) resistance to 5-fluorouracil (5FU) and oxaliplatin (OXP).
  • To elucidate the underlying molecular mechanisms, specifically the involvement of the Notch signaling pathway.

Main Methods:

  • Bioinformatic analysis of CSF2 expression in CRC and its prognostic impact.
  • Cell viability (CCK-8 assay), apoptosis (flow cytometry), and gene/protein expression (qRT-PCR, western blot) were assessed.
  • Gene Set Enrichment Analysis (GSEA) and Notch pathway modulation (using Jagged-1 activator) were employed to explore CSF2's mechanism.

Main Results:

  • High CSF2 expression is associated with poor CRC prognosis.
  • CSF2 downregulation was observed in chemoresistant CRC cells; CSF2 silencing reduced resistance, decreased cell survival, and promoted apoptosis.
  • CSF2 activates the Notch signaling pathway, which is upregulated in resistant cells; silencing CSF2 inhibited this pathway, and Jagged-1 reversed these effects.

Conclusions:

  • Silencing CSF2 inhibits colorectal cancer (CRC) cell resistance to 5-fluorouracil (5FU) and oxaliplatin (OXP).
  • This inhibition is mediated through the regulation of the Notch signaling pathway.
Keywords:
CSF2Colorectal cancerNotch pathwayResistance

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