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Updated: Oct 13, 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

MDR 1 activation is the predominant resistance mechanism selected by vinblastine in MES-SA cells

G K Chen1, G E Durán, A Mangili

  • 1Oncology Division, Department of Medicine, and the Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305-5151, USA.

British Journal of Cancer
|September 6, 2000
PubMed

Insights

Spontaneous mutations drive vinblastine resistance in sarcoma cells, activating the MDR1 gene. This leads to a stable multidrug resistance phenotype, crucial for understanding cancer treatment strategies.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Drug Resistance Mechanisms

Background:

  • Understanding drug resistance is crucial for effective cancer chemotherapy.
  • Vinblastine is a key chemotherapeutic agent used in treating various cancers.
  • The human sarcoma cell line MES-SA is a relevant model for studying drug resistance.

Purpose of the Study:

  • To investigate the mechanisms of cellular resistance to vinblastine in MES-SA cells.
  • To determine mutation rates associated with vinblastine resistance.
  • To characterize the multidrug resistance phenotype in selected clones.

Main Methods:

  • Single-step selection of MES-SA cells using vinblastine.
  • Fluctuation analysis to assess mutation rates.
  • Phenotypic characterization of resistant clones for drug cross-resistance.
  • Analysis of gene expression (MDR1, mrp) and protein function (P-glycoprotein).

Main Results:

  • A mutation rate of 7 x 10(-7) per cell generation was observed under stringent vinblastine selection.
  • Spontaneous mutations, not adaptive responses, were identified as conferring resistance.
  • Resistant clones exhibited stable multidrug resistance to vinblastine and paclitaxel.
  • Activation of MDR1 gene expression and P-glycoprotein function was confirmed in all resistant clones.

Conclusions:

  • Initial vinblastine resistance in MES-SA cells arises from stochastic mutation events.
  • Activation of the MDR1 gene is a common mechanism in these mutants.
  • The stable multidrug resistance phenotype has implications for therapeutic strategies.

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