title: Using rhodamine 123 accumulation in CD8 cells as a surrogate indicator to study the P-glycoprotein modulating effect of cepharanthine hydrochloride in vivo.
abstract: 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.
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Zhenzhou 45001, Henan, China.
authors.forename: Han
authors.initials: H
authors.lastname: Li
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yan
authors.forename: Wang
authors.initials: W
authors.lastname: Ning
authors.forename: Guo
authors.initials: G
authors.lastname: Xiao-Juan
authors.forename: Zang
authors.initials: Z
authors.lastname: Cai-Hong
authors.forename: Jiang
authors.initials: J
authors.lastname: Jin-Hua
authors.forename: Ma
authors.initials: M
authors.lastname: Fang
authors.forename: Wang
authors.initials: W
authors.lastname: Qing-Duan
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D016572:Cyclosporine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005456:Fluorescent Dyes / Q000032:analysis / Q000737:chemistry; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007202:Indicators and Reagents / Q000032:analysis; D008113:Liver Neoplasms / Q000188:drug therapy; D051379:Mice; D020112:Rhodamine 123 / Q000032:analysis* / Q000737:chemistry; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D052117:Benzodioxoles
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044182:Benzylisoquinolines; D016572:Cyclosporine; D004317:Doxorubicin; D005456:Fluorescent Dyes; D005472:Fluorouracil; D007202:Indicators and Reagents; D020112:Rhodamine 123; D014700:Verapamil; C006947:cepharanthine; D052117:Benzodioxoles