Using Rhodamine 123 Accumulation inCD8+Cells as a Surrogate Indicator to Study the P-Glycoprotein Modulating Effect of Cepharanthine Hydrochloride In Vivo

[摘要] The purpose of this study was the use of rhodamine 123 (Rho123) accumulation in peripheral bloodCD8+cells as a surrogate indicator to evaluate the modulating effect of P-glycoprotein (P-gp) inhibitors in the multidrug resistance (MDR) tumor-bearing mouse model. Rho123 was administered to mice, and the fluorescence level inCD8+cells was measured. Cepharanthine hydrochloride (CH) and verapamil (VER), two P-gp inhibitors, were administered to mice 1 hour prior to Rho123 administrationin vivoor added to peripheral blood 1 hour prior to Rho123 additionex vivo. The tumor inhibition effect of 5-fluorouracil/adriamycin/cisplatin (FAP) protocol plus CH was also investigated. A concentration- or dose-response relationship was shown between the concentration and dose of CH and Rho123 accumulation or the antitumor activity. In conclusion, the measurement of Rho123 accumulation inCD8+cells provides a surrogate assay for the screening of candidate P-gp inhibitors in preclinical trials, and CH is effective in modulating P-gp-mediated MDRin vivo.

[学科分类] 基础医学