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Updated: Aug 11, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Intercellular transfer of drug resistance

O S Frankfurt1, D Seckinger, E V Sugarbaker

  • 1Oncology Laboratory, Cedars Medical Center, Miami, Florida 33136.

Cancer Research
|February 15, 1991
PubMed

Insights

Sensitive cells gain drug resistance when co-cultured with resistant cells, due to glutathione transfer. Inhibiting this cell cooperation may enhance chemotherapy effectiveness.

Area of Science:

  • Cell biology
  • Cancer research
  • Pharmacology

Background:

  • Chemotherapy resistance in cancer is a major clinical challenge.
  • Understanding mechanisms of drug resistance transfer is crucial for improving treatment outcomes.

Purpose of the Study:

  • To investigate the effect of L-phenylalanine mustard (L-PAM) on heterogeneous cell populations.
  • To elucidate the role of intercellular communication in acquired drug resistance.

Main Methods:

  • Flow cytometric analysis of DNA damage induced by L-PAM.
  • Co-culture experiments with sensitive and resistant cell lines.
  • Colony formation assays.
  • Measurement of glutathione (GSH) content.

Main Results:

  • DNA damage was reduced in sensitive cells co-cultured with resistant cells, indicating acquired resistance.
  • This resistance transfer was dependent on direct cell contact and inhibited by phorbol ester.
  • Glutathione (GSH) transfer from resistant to sensitive cells was identified as the mechanism for decreased DNA damage.
  • Co-culture also conferred resistance to Adriamycin, demonstrating multiclass drug resistance.

Conclusions:

  • Intercellular transfer of GSH from resistant to sensitive cells mediates drug resistance.
  • Metabolic cooperation between distinct cell populations can induce multiclass drug resistance.
  • Inhibiting cell cooperation presents a potential strategy to improve tumor response to combination chemotherapy.

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