CONTINUOUS IN-SITU ELECTROCHEMICAL MONITORING OF DOXORUBICIN EFFLUX FROM SENSITIVE AND DRUG-RESISTANT CANCER-CELLS

One of the least well understood problems in cancer chemotherapy is th e cross-resistance of certain tumor cells to a series of chemically un related drugs. Multidrug resistance (MDR) can be attributed to several different biophysical processes, among them increased drug efflux. Th is has been found to correlate with overexpression of the cell surface 170-kDa P-glycoprotein that actively excludes cytotoxic drugs against their concentration gradient. To better understand MDR, experimental methods are needed to study drug efflux from cancer cells. Continuous measurement of efflux of nonfluorescent drugs on the same cell culture in situ, or assessing efflux from a few cells or even a single cell, is beyond the capabilities of existing technologies. In this work, a c arbon fiber (CF) microelectrode is used to monitor efflux of doxorubic in from a monolayer of two cell lines: an auxotrophic mutant of Chines e hamster ovary cells, AUXB1, and its MDR subline, CH(R)C5. Because do xorubicin is both fluorescent and electroactive, the results could be validated against existing data obtained optically and with other tech niques on the same cell lines, with good agreement found. The electroc hemical detection, however, is capable of in situ monitoring with high temporal resolution and is suitable for single-cell studies.