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Updated: Aug 11, 2026

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method
16:07

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method

Published on: September 16, 2017

Adenovirus-mediated wild-type-p53-gene expression sensitizes TNF-resistant tumor cells to TNF-induced cytotoxicity by

V A Shatrov1, M Ameyar, C Bouquet

  • 1INSERM U487, "Cytokines et Immunologie des Tumeurs Humaines," Institut Gustave Roussy, Villejuif, France.

International Journal of Cancer
|December 10, 1999
PubMed

Insights

Restoring wild-type p53 (wt-p53) function in tumor cells enhances their sensitivity to tumor necrosis factor (TNF)-induced cell death. This occurs through reactive oxygen intermediates (ROIs) production, highlighting a new therapeutic strategy for p53-deficient cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Loss of p53 function confers resistance to tumor necrosis factor (TNF)-induced cytotoxicity.
  • Understanding mechanisms of TNF resistance is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To investigate the effect of wild-type p53 (wt-p53) expression on TNF sensitivity in p53-deleted MCF7/Adr cells.
  • To elucidate the role of reactive oxygen intermediates (ROIs) and glutathione (GSH) in p53-mediated sensitization to TNF.

Main Methods:

  • Introduction of wt-p53 into MCF7/Adr cells using a recombinant adenovirus (Ad-p53).
  • Assessment of cell viability, ROIs production, GSH levels, and MnSOD mRNA expression.
  • Treatment with N-acetylcysteine (NAC) to evaluate the role of redox state.

Main Results:

  • Ad-p53 infection sensitized MCF7/Adr cells to TNF-induced death at low viral particle concentrations.
  • wt-p53 expression induced ROIs production and GSH depletion, altering the cellular redox state.
  • NAC treatment partially reversed p53-induced sensitization to TNF, and Ad-p53 inhibited TNF-induced MnSOD mRNA expression.

Conclusions:

  • Wild-type p53 expression sensitizes TNF-resistant MCF7 cells with p53 deletion to TNF-induced cell death.
  • This sensitization is mediated by a pathway involving ROIs production and potentially modulated by MnSOD expression.
  • Targeting the p53-redox axis presents a potential strategy for overcoming TNF resistance in cancer.

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