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Using rhodamine 123 accumulation in [CD8.sup.+] cells as a surrogate indicator to study the P-glycoprotein modulating effect of cepharanthine hydrochloride in vivo
- Source :
- Journal of Biomedicine and Biotechnology. Annual 2011
- Publication Year :
- 2011
-
Abstract
- 1. Introduction Multidrug resistance (MDR) remains the major obstacle to success in a wide variety of advanced malignancies, particularly in solid cancers. The overexpression of P-gp is one of the [...]<br />The purpose of this study was the use of rhodamine 123 (Rho123) accumulation in peripheral blood [CD8.sup.+] 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.sup.+] 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.sup.+] 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.
Details
- Language :
- English
- ISSN :
- 11107243
- Database :
- Gale General OneFile
- Journal :
- Journal of Biomedicine and Biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.266629799
- Full Text :
- https://doi.org/10.1155/2011/281651