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Exp Ther Med. 2017 Feb;13(2):437-442. doi: 10.3892/etm.2016.4011. Epub 2016 Dec 29.

Geniposide reverses multidrug resistance in vitro and in vivo by inhibiting the efflux function and expression of P-glycoprotein.

Author information

1
Department of Pharmacy, Yichang Central People's Hospital, First Affiliated Hospital of China Three Gorges University, Yichang, Hubei 443002, P.R. China.
2
Department of Pharmacy, Medical College of China Three Gorges University, Yichang, Hubei 443002, P.R. China.

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.

KEYWORDS:

P-glycoprotein; geniposide; multidrug resistance; tumor xenograft

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