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Dioscin enhances methotrexate absorption by down-regulating MDR1 in vitro and in vivo.
Wang, Lijuan; Wang, Changyuan; Peng, Jinyong; Liu, Qi; Meng, Qiang; Sun, Huijun; Huo, Xiaokui; Sun, Pengyuan; Yang, Xiaobo; Zhen, Yuhong; Liu, Kexin.
Afiliación
  • Wang L; Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, PR China. Electronic address: jlwang1979@163.com.
  • Wang C; Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, PR China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, PR China. Electronic address: wangcyuan@163.com.
  • Peng J; Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, PR China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, PR China. Electronic address: jinyongpeng2005@163.com.
  • Liu Q; Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, PR China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, PR China. Electronic address: llaqii@yahoo.com.cn.
  • Meng Q; Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, PR China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, PR China. Electronic address: mengq531@yahoo.cn.
  • Sun H; Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, PR China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, PR China. Electronic address: sunhuijun@hotmail.com.
  • Huo X; Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, PR China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, PR China. Electronic address: huoxiaokui@163.com.
  • Sun P; Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, PR China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, PR China. Electronic address: spfar1004@gmail.com.
  • Yang X; Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, PR China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, PR China. Electronic address: bocai789770@163.com.
  • Zhen Y; Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, PR China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, PR China. Electronic address: zhenyhwaner@yahoo.com.cn.
  • Liu K; Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, Liaoning, PR China; Provincial Key Laboratory for Pharmacokinetics and Transport, Liaoning, Dalian Medical University, Dalian, Liaoning, PR China. Electronic address: kexinliu@dlmedu.edu.cn.
Toxicol Appl Pharmacol ; 277(2): 146-54, 2014 Jun 01.
Article en En | MEDLINE | ID: mdl-24680847
The purpose of this study was to investigate the enhancing effect of dioscin on the absorption of methotrexate (MTX) and clarify the molecular mechanism involved in vivo and in vitro. Dioscin increased MTX chemosensitivity and transepithelial flux in the absorptive direction, significantly inhibiting multidrug resistance 1 (MDR1) mRNA and protein expression and MDR1 promoter and nuclear factor κ-B (NF-κB) activities in Caco-2 cells. Moreover, inhibitor κB-α (IκB-α) degradation was inhibited by dioscin. Dioscin enhanced the intracellular concentration of MTX by down-regulating MDR1 expression through a mechanism that involves NF-κB signaling pathway inhibition in Caco-2 cells. Dioscin strengthened MTX absorption by inhibiting MDR1 expression in rat intestine. In addition, even though MTX is absorbed into the enterocytes, there was no increase in toxicity observed, and that, in fact, decreased toxicity was seen.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metotrexato / Miembro 1 de la Subfamilia B de Casetes de Unión a ATP / Subfamilia B de Transportador de Casetes de Unión a ATP / Enterocitos / Diosgenina / Absorción Intestinal / Intestino Delgado / Antimetabolitos Antineoplásicos Límite: Animals / Humans / Male Idioma: En Revista: Toxicol Appl Pharmacol Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metotrexato / Miembro 1 de la Subfamilia B de Casetes de Unión a ATP / Subfamilia B de Transportador de Casetes de Unión a ATP / Enterocitos / Diosgenina / Absorción Intestinal / Intestino Delgado / Antimetabolitos Antineoplásicos Límite: Animals / Humans / Male Idioma: En Revista: Toxicol Appl Pharmacol Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos