Using Rhodamine 123 Accumulation in CD8+ Cells as a Surrogate Indicator to Study the P-Glycoprotein Modulating Effect of Cepharanthine Hydrochloride In Vivo

• Main Authors: Han Li, Zhang Yan, Wang Ning, Guo Xiao-Juan, Zang Cai-Hong, Jiang Jin-Hua, Ma Fang, Wang Qing-Duan
• Format: Article
• Language: English
• Published: Hindawi Limited 2011-01-01
• Series: Journal of Biomedicine and Biotechnology
• Online Access: http://dx.doi.org/10.1155/2011/281651

The purpose of this study was the use of rhodamine 123 (Rho123) accumulation in peripheral blood CD8+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 in CD8+ cells was measured. Cepharanthine hydrochloride (CH) and verapamil (VER), two P-gp inhibitors, were administered to mice 1 hour prior to Rho123 administration in vivo or added to peripheral blood 1 hour prior to Rho123 addition ex 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 in CD8+ 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 MDR in vivo.