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Sen-Ling Feng,Hai-Bin Luo,Liang Cai,Jie Zhang,Dan Wang,Ying-Jiang Chen,Huan-Xing Zhan,Zhi-Hong Jiang,Ying Xie 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.2
Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinicalcancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediatedby ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrateswere carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. Theexpressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cellxenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation ofABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPaseand reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 bindingsite which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 anddocetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizingeffect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXTtreatment significantly suppressed the growth of drug-resistant tumors without increase in toxicitywhen compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvantchemotherapy, which encourages further pharmacokinetic and clinical studies.
Feng, Sen-Ling,Luo, Hai-Bin,Cai, Liang,Zhang, Jie,Wang, Dan,Chen, Ying-Jiang,Zhan, Huan-Xing,Jiang, Zhi-Hong,Xie, Ying The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.2
Background: 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. Methods: 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. Results: 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 the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.