Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention

Br J Cancer. 2019 Feb;120(4):407-423. doi: 10.1038/s41416-018-0301-9. Epub 2019 Feb 4.


Background: Emergence of drug-resistant cancer phenotypes is a challenge for anti-cancer therapy. Cancer stem cells are identified as one of the ways by which chemoresistance develops.

Method: We investigated the anti-inflammatory combinatorial treatment (DA) of doxorubicin and aspirin using a preclinical microfluidic model on cancer cell lines and patient-derived circulating tumour cell clusters. The model had been previously demonstrated to predict patient overall prognosis.

Results: We demonstrated that low-dose aspirin with a sub-optimal dose of doxorubicin for 72 h could generate higher killing efficacy and enhanced apoptosis. Seven days of DA treatment significantly reduced the proportion of cancer stem cells and colony-forming ability. DA treatment delayed the inhibition of interleukin-6 secretion, which is mediated by both COX-dependent and independent pathways. The response of patients varied due to clinical heterogeneity, with 62.5% and 64.7% of samples demonstrating higher killing efficacy or reduction in cancer stem cell (CSC) proportions after DA treatment, respectively. These results highlight the importance of using patient-derived models for drug discovery.

Conclusions: This preclinical proof of concept seeks to reduce the onset of CSCs generated post treatment by stressful stimuli. Our study will promote a better understanding of anti-inflammatory treatments for cancer and reduce the risk of relapse in patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / administration & dosage*
  • Apoptosis / drug effects
  • Aspirin / administration & dosage*
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage*
  • Drug Therapy, Combination
  • Epithelial-Mesenchymal Transition / drug effects
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / physiology
  • Microfluidics
  • Neoplasm Recurrence, Local / prevention & control*
  • Neoplastic Stem Cells / drug effects*
  • Prostaglandin-Endoperoxide Synthases / physiology
  • Signal Transduction / drug effects


  • Anti-Inflammatory Agents
  • Interleukin-6
  • Doxorubicin
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin