Geniposide reverses multidrug resistance in vitro and in vivo by 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.