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: Han Li, Zhang Yan, Wang Ning, Guo Xiao-Juan, Zang Cai-Hong, Jiang Jin-Hua, Ma Fang, Wang Qing-Duan
• Journal: Journal of biomedicine & biotechnology (J Biomed Biotechnol) Vol. 2011 Pg. 281651 ( 2011) ISSN: 1110-7251 [Electronic] United States
• PMID: 21765632 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Benzylisoquinolines
• Fluorescent Dyes
• Indicators and Reagents
• Rhodamine 123
• cepharanthine
• Doxorubicin
• Cyclosporine
• Verapamil
• Fluorouracil

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (antagonists & inhibitors)
• Animals
• Benzylisoquinolines (pharmacology)
• CD8-Positive T-Lymphocytes (cytology, metabolism)
• Carcinoma, Hepatocellular (drug therapy)
• Cyclosporine (therapeutic use)
• Dose-Response Relationship, Drug
• Doxorubicin (therapeutic use)
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Fluorescent Dyes (analysis, chemistry)
• Fluorouracil (therapeutic use)
• Humans
• Indicators and Reagents (analysis)
• Liver Neoplasms (drug therapy)
• Mice
• Rhodamine 123 (analysis, chemistry)
• Tumor Cells, Cultured
• Verapamil (pharmacology)
• Xenograft Model Antitumor Assays