Ginsenoside Rg5 overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter: in vitro and in vivo study

Journal of Ginseng Research
Sen-Ling FengYing Xie

Abstract

Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo. Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed th...Continue Reading

Citations

May 17, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ahmed M MetwalyDou Deqiang
Oct 13, 2020·Frontiers in Pharmacology·Sandrine L VerstraetenMarie-Paule Mingeot-Leclercq
Jun 22, 2021·Experimental and Therapeutic Medicine·Ming-Yang LiuHai-Jun Li

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Methods Mentioned

BETA
flow cytometry
xenograft
electrophoresis
xenografts

Software Mentioned

Surflex
CalcuSyn
- dock
Tripos Sybyl X
Quantity One
GraphPad Prism
FlowJo

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