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Drug retention, efflux, and resistance in tumor cells
A Krishan1, C M Fitz, I Andritsch
1Radiation Oncology Department, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Florida 33101, USA.
Abstract:
Multiple drug resistance (MDR) in tumor cells has been related to the expression of transport proteins which alter cellular drug transport and distribution. Three different genes (mdr, MRP, and LRP) and their products have been implicated in MDR. Several fluorescent dyes have been used to monitor the effect of these transport proteins on drug retention, as well as for screening of drugs which block drug efflux and thus enhance cellular drug retention and cytotoxicity. The present review summarizes current knowledge about MDR phenotypic markers and techniques available for study of MDR by flow cytometry.
Insights
Multiple drug resistance (MDR) in tumor cells involves transport proteins affecting drug distribution. This review covers MDR markers and flow cytometry techniques for studying drug efflux and retention.
Area of Science:
- Biochemistry and Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Multiple drug resistance (MDR) in tumor cells is a significant challenge in cancer therapy.
- MDR is often mediated by efflux pump proteins encoded by genes like mdr, MRP, and LRP.
- These proteins alter intracellular drug concentrations, reducing therapeutic efficacy.
Purpose of the Study:
- To review current knowledge on MDR phenotypic markers.
- To summarize techniques for studying MDR, particularly flow cytometry.
- To highlight the role of transport proteins in drug resistance and potential therapeutic strategies.
Main Methods:
- Utilizing fluorescent dyes to monitor drug retention in cells expressing MDR proteins.
- Employing flow cytometry as a key technique for analyzing drug transport and efflux.
- Reviewing literature on genetic and protein-based markers associated with MDR.
Main Results:
- Expression of mdr, MRP, and LRP genes and their protein products are key indicators of MDR.
- Fluorescent dyes effectively visualize the impact of efflux pumps on drug retention.
- Flow cytometry provides a sensitive platform for assessing MDR phenotypes and screening modulators.
Conclusions:
- Understanding MDR mechanisms through phenotypic markers and flow cytometry is crucial for developing effective cancer treatments.
- Targeting drug efflux pumps offers a promising strategy to overcome MDR.
- Further research using these techniques can aid in the development of novel chemotherapeutic agents.