Laser flow cytometry (FCM) offers a unique tool for monitoring of fluorescent antitumor drug retention and its modulation in tumor cells. Besides its rapidity, the laser FCM method can identify heterogeneity of drug retention as well as allow for sorting of subpopulations for further biochemical or morphological characterization. Cellular resistance to some of the clinically important anthracyclines has been suggested to be due to rapid drug efflux. Thus, drugs that block anthracycline efflux and thereby enhance retention can reduce cellular resistance to anthracyclines. Laser FCM is used to monitor anthracycline fluorescence in tumor cells and to monitor the effect of drug efflux blocking agents on drug retention. This method is also used to monitor anthracycline retention and its modulation by phenothiazines and amphotericin-B in P388 and doxorubicin-resistant cells. Some data show that the effect of efflux blockers on doxorubicin retention is cell-cycle proliferation related, and often one can identify subpopulations based on their differential response to efflux blockers. From these studies it follows that modulation of drug transport and thereby cellular resistance by phenothiazines or calcium channel blockers may not be uniform in a population but may be selective and confined to only certain types of cells and subpopulations.
ASJC Scopus subject areas
- Cell Biology