Modulation of P-glycoprotein activity by estramustine is limited by binding to plasma proteins

摘要: Background. Estramustine previously has been shown to interact with P-glycoprotein and restore intracellular accumulation of vinblastine paclitaxel in cells overexpressing this drug transporter. However, the ability estramustine potentiate cytotoxicities several drugs was less than that expected. To resolve apparent discordance, authors examined effects serum on actions estramustine. Methods. The anticancer or without verapamil toward MCF-7 breast carcinoma a P-glycoprotein-overexpressing subline MCF-7/ADR were determined using sulforhodamine-binding assay. extent [ 3 H]vinblastine H]paclitaxel for each standard methods, binding radiolabeled plasma proteins characterized by equilibrium dialysis. Results. Without serum, sensitivities P-glycoprotein-transported increased verapamil. Conversely, when treated 10% these verapamil, but not markedly ; however, suppressed much more strongly those Equilibrium dialysis experiments demonstrated H]estramustine binds proteins, predominantly albumin, whereas albumin alpha 1 -acid-glycoprotein, alpha-acid-glycoprotein. Conclusion. Although can bind P-glycoprotein, its effectiveness as reversing agent vivo likely is limited proteins. Cancer 1995 ;75 :2597-2604.