Related Experiment Video

Updated: Jul 17, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Targeting transforming growth factor beta (TGF-β) using Pirfenidone, a potential repurposing therapeutic strategy in

Hamid Jamialahmadi1,2,3, Seyedeh Elnaz Nazari1, Hamid TanzadehPanah1,2,4

  • 1Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Scientific Reports
|September 1, 2023
PubMed

Insights

Pirfenidone (PFD), a transforming growth factor beta (TGF-β) inhibitor, suppressed colorectal cancer (CRC) cell proliferation and migration. PFD combined with 5-fluorouracil (5-FU) shows potential for enhanced CRC treatment.

Area of Science:

  • Oncology
  • Cancer Biology
  • Pharmacology

Background:

  • The tumor microenvironment, including transforming growth factor beta (TGF-β), can limit colorectal cancer (CRC) treatment efficacy.
  • TGF-β signaling plays a critical role in CRC progression, proliferation, and metastasis.

Purpose of the Study:

  • To investigate the therapeutic potential of Pirfenidone (PFD), a TGF-β inhibitor, in preclinical colorectal cancer models.
  • To evaluate PFD alone and in combination with 5-fluorouracil (5-FU) for anti-tumor activity in CRC.

Main Methods:

  • In vitro assessment of PFD's anti-proliferative and anti-migratory effects using MTT and wound-healing assays.
  • In vivo evaluation of PFD's anti-tumor activity, histopathology, and side effects in CRC xenograft models.
  • Analysis of molecular markers including survivin, MMP9, E-cadherin, and collagen.

Main Results:

  • PFD significantly suppressed CRC cell proliferation and migration, modulating survivin and MMP9/E-cadherin.
  • PFD inhibited TGF-β-induced tumor progression, fibrosis, and inflammation by affecting collagen and E-cadherin.
  • The combination of PFD and 5-FU demonstrated enhanced anti-tumor effects compared to monotherapy.

Conclusions:

  • Targeting the TGF-β pathway with PFD shows promise in reducing CRC cell proliferation and migration.
  • PFD, particularly in combination with 5-FU, may offer a novel therapeutic strategy to improve CRC treatment outcomes.
  • Inhibition of TGF-β signaling by PFD can mitigate tumor progression and associated stromal changes in CRC.

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