Flow cytometric monitoring of drug resistance in human tumor cells.
Recent studies have identified a family of glycoproteins which modulate cellular transport of antibiotics, alkaloids and drugs used in cancer chemotherapy. By facilitating efflux of drugs from the intracellular domain, these proteins reduce cytotoxicity and thus confer drug resistance. With the availability of antibodies raised against these phenotypic markers of drug resistance, immunohistochemistry and flow cytometry has been used to study their distribution and expression in normal and tumor cells. As some of the drugs used in cancer chemotherapy and other dyes which are substrates for this efflux pump are fluorescent, laser flow cytometry can be used for rapid quantitation of cellular retention, efflux and heterogeneity in drug transport of a tumor cell population. This method can also be used to screen drugs which may block efflux of a chemotherapeutic drug and thus increase chemosensitivity of a drug resistant tumor. In the present report flow cytometric methods for the study of drug transport and its modulation in tumor cells are discussed.
Krishan
Awtar
A
Division of Experimental Therapeutics, University of Miami Medical School, Miami, FL 33101, USA. akrishan@med.miami.edu
D001692:Biological Transport / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*