Calmodulin inhibitor trifluoperazine in combination with doxorubicin induces the selection of tumour cells with the multidrug resistant phenotype
1993

Trifluoperazine and Doxorubicin: Inducing Drug Resistance in Cancer Cells

publication Evidence: moderate

Author Information

Author(s): N. Kamath, D. Grabowski, J. Ford, R. Ganapathi

Primary Institution: Cleveland Clinic Foundation

Hypothesis

Can trifluoperazine in combination with doxorubicin induce the selection of multidrug resistant tumor cells?

Conclusion

The study found that trifluoperazine combined with low doses of doxorubicin can lead to the selection of tumor cells that are over 30 times more resistant to the drug.

Supporting Evidence

  • Trifluoperazine combined with doxorubicin led to a significant increase in drug resistance in L1210 mouse leukemia cells.
  • L1210/DT cells showed over 30-fold resistance to doxorubicin after treatment with trifluoperazine.
  • Drug accumulation studies indicated that L1210/DT cells retained less doxorubicin compared to sensitive cells.

Takeaway

This study shows that a drug called trifluoperazine can help cancer cells become resistant to another drug called doxorubicin, making it harder to treat the cancer.

Methodology

L1210 mouse leukemia cells were treated with doxorubicin and trifluoperazine, and their resistance was assessed through cytotoxicity assays and drug accumulation studies.

Limitations

The study primarily focuses on a specific cell line and may not fully represent the complexity of drug resistance in all cancer types.

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