MDR 1 activation is the predominant resistance mechanism selected by vinblastine in MES-SA cells
2000
Vinblastine Resistance in Cancer Cells
publication
Author Information
Author(s): Chen G K, Durán G E, Mangili A, Beketic-Oreskovic L, Sikic B I
Primary Institution: Stanford University School of Medicine
Hypothesis
Spontaneous mutations confer vinblastine resistance rather than induction of adaptive response elements.
Conclusion
The study found that vinblastine-selected mutants develop resistance primarily through stochastic mutations activating the MDR 1 gene.
Supporting Evidence
- The mutation rate was found to be 7 × 10–7 per cell generation.
- Surviving clones displayed a stable multidrug resistance phenotype over a 3-month period.
- All propagated clones demonstrated high levels of resistance to vinblastine and paclitaxel.
Takeaway
When cancer cells are exposed to vinblastine, they can change and become resistant to the drug, mainly due to random changes in their genes.
Methodology
Single-step selection with vinblastine was performed in populations of the human sarcoma cell line MES-SA to assess resistance mechanisms and mutation rates.
Digital Object Identifier (DOI)
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