Drug extrusion, I-125(-) efflux and the control of intracellular [Ca2+] indrug-resistant ovarian epithelial cells

Experiments were undertaken using an ovarian adenocarcinoma cell line (A278 0) and a drug-resistant strain (A2780.ad) derived from this line. P-glycopr otein could not be detected in A2780 cells but was essentially ubiquitous i n A2780.ad cells, although removing the selective pressure for drug resista nce led to reduced expression. However, the amount of P-glycoprotein presen t was used to predict the capacity of these cells to extrude rhodamine-123 (R-123) and their resistance to adriamycin, a cytotoxic drug. This accords with the role of P-glycoprotein as a drug pump. Although hypotonic solution s increased anion efflux from A2780 and A2780.ad cells, larger responses oc curred in the parental line. Moreover, R-123 extrusion and anion efflux app eared to be mutually independent processes and so these data do not support the view that P-glycoprotein is involved in the control of volume-sensitiv e anion channels. Hypotonic solutions increased intracellular free calcium ([Ca2+](i)) in drug-resistant cells but not in the parental line, and so es tablishing a drug-resistant strain may affect the control of [Ca2+](i) duri ng osmotic swelling. This could account for effects that were previously at tributed to P-glycoprotein.