title: Geniposide reverses multidrug resistancein vitroandin vivoby inhibiting the efflux function and expression of P-glycoprotein.
abstract: Geniposide is a water-soluble iridoid glucoside with anti-oxidant and anti-inflammatory biological functions. It has been indicated that geniposide may increase doxorubicin (DOX) accumulation in drug-resistant tumor cells. The present study aimed to investigate the resistance-reversing effect of geniposide in DOX-resistant cells and assess the underlying mechanisms of its action. The results revealed that geniposide itself weakly inhibited tumor cell growth. Furthermore, geniposide effectively reversed DOX resistance in a dose-dependent manner in human osteosarcoma DOX-resistant (MG63/DOX) cells. The action of geniposide was confirmed by increased accumulation of intracellular DOX detected in MG63/DOX cells. Notably, geniposide enhanced the efficacy of DOX against MG63/DOX cancer cell-derived xenografts in nude mice. To study the mechanism, intracellular accumulation of rhodamine 123 was measured using flow cytometry. At concentrations that reversed multidrug resistance (MDR), geniposide significantly downregulated P-glycoprotein (P-gp) expression. Therefore, geniposide reverses P-gp-mediated MDR by reducing the expression of P-gp and its transport function. The present study therefore indicated that geniposide may be administered in combination with conventional anti-neoplastic drugs to prevent MDR.
authors.affiliation: Department of Pharmacy, Yichang Central People's Hospital, First Affiliated Hospital of China Three Gorges University, Yichang, Hubei 443002, P.R. China.
authors.forename: Hefei
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, Yichang Central People's Hospital, First Affiliated Hospital of China Three Gorges University, Yichang, Hubei 443002, P.R. China.
authors.forename: Xuenong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Yichang Central People's Hospital, First Affiliated Hospital of China Three Gorges University, Yichang, Hubei 443002, P.R. China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, Yichang Central People's Hospital, First Affiliated Hospital of China Three Gorges University, Yichang, Hubei 443002, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Medical College of China Three Gorges University, Yichang, Hubei 443002, P.R. China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhou
keywords: P-glycoprotein; geniposide; multidrug resistance; tumor xenograft