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Differential preventive activity of sulindac and atorvastatin in Apc+/Min-FCCCmice with or without colorectal adenomas

  • 0Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
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November 11, 2017

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November 11, 2017

View abstract on PubMed

Summary

This summary is machine-generated.

Chemopreventive agent efficacy varies based on colorectal tumour status. Atorvastatin prevented microadenomas in tumour-free mice, while sulindac/atorvastatin combination therapy reduced tumours in existing tumour-bearing mice.

Area Of Science

  • Oncology
  • Gastroenterology
  • Pharmacology

Background

  • Individual responses to cancer preventive interventions are highly variable.
  • Understanding how pre-existing tumour status affects chemopreventive efficacy is crucial for personalized medicine.

Purpose Of The Study

  • To investigate if the effectiveness of a chemopreventive agent differs between animals without colorectal tumours and those with existing tumours.
  • To evaluate the combined effect of sulindac and atorvastatin in a colorectal cancer model.

Main Methods

  • Apc<sup>+/Min-FCCC</sup> mice were treated with sulindac, atorvastatin, or both, with known tumour status at treatment initiation.
  • Histopathology and gene expression analyses were performed after 14 weeks and 7 days of treatment, respectively.
  • Cell cycle analysis was conducted on SW480 colon carcinoma cells treated with the agents.

Main Results

  • Atorvastatin completely inhibited microadenoma formation in tumour-free mice and altered stem/progenitor cell gene expression.
  • Sulindac/atorvastatin combination therapy reduced colorectal adenoma multiplicity by 43% in tumour-bearing mice.
  • Combination therapy induced cell cycle arrest (G0/G1) in colon cancer cells and modulated key genes like Hoxb13 and Rprm.

Conclusions

  • An animal's tumour status at the start of treatment significantly influences its response to chemoprevention.
  • Atorvastatin demonstrated efficacy in preventing early-stage tumour development.
  • The combination of sulindac and atorvastatin showed superior tumour inhibition in established tumour models compared to individual agents.

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