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Sinomenine sensitizes multidrug-resistant colon cancer cells (Caco-2) to doxorubicin by downregulation of MDR-1 expression

Chemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that sinomenine can enhance the absorption of various P-gp substrates. In the prese... Full description

Journal Title: PloS one 2014, Vol.9(6), pp.e98560
Main Author: Liu, Zhen
Other Authors: Duan, Zhi-Jun , Chang, Jiu-Yang , Zhang, Zhi-Feng , Chu, Rui , Li, Yu-Ling , Dai, Ke-Hang , Mo, Guang-Quan , Chang, Qing-Yong
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1932-6203 ; PMID: 24901713 Version:1 ; DOI: 10.1371/journal.pone.0098560
Link: http://pubmed.gov/24901713
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recordid: medline24901713
title: Sinomenine sensitizes multidrug-resistant colon cancer cells (Caco-2) to doxorubicin by downregulation of MDR-1 expression
format: Article
creator:
  • Liu, Zhen
  • Duan, Zhi-Jun
  • Chang, Jiu-Yang
  • Zhang, Zhi-Feng
  • Chu, Rui
  • Li, Yu-Ling
  • Dai, Ke-Hang
  • Mo, Guang-Quan
  • Chang, Qing-Yong
subjects:
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 -- Genetics
  • Antibiotics, Antineoplastic -- Pharmacology
  • Doxorubicin -- Pharmacology
  • Drug Resistance, Multiple -- Genetics
  • Drug Resistance, Neoplasm -- Genetics
  • Gene Expression Regulation, Neoplastic -- Drug Effects
  • Morphinans -- Pharmacology
ispartof: PloS one, 2014, Vol.9(6), pp.e98560
description: Chemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that sinomenine can enhance the absorption of various P-gp substrates. In the present study, we investigated the effect of sinomenine on the chemoresistance in colon cancer cells and explored the underlying mechanism. We developed multidrug-resistant Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1 genes as well as activation of the NF-κB signal pathway in MDR-Caco-2 cells. Importantly, we found that sinomenine enhances the sensitivity of MDR-Caco-2 cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through inhibition of the NF-κB signaling pathway. These findings provide a new potential strategy for the reversal of P-gp-mediated anticancer drug resistance....
language: eng
source:
identifier: E-ISSN: 1932-6203 ; PMID: 24901713 Version:1 ; DOI: 10.1371/journal.pone.0098560
fulltext: fulltext
issn:
  • 19326203
  • 1932-6203
url: Link


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titleSinomenine sensitizes multidrug-resistant colon cancer cells (Caco-2) to doxorubicin by downregulation of MDR-1 expression
creatorLiu, Zhen ; Duan, Zhi-Jun ; Chang, Jiu-Yang ; Zhang, Zhi-Feng ; Chu, Rui ; Li, Yu-Ling ; Dai, Ke-Hang ; Mo, Guang-Quan ; Chang, Qing-Yong
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subjectATP Binding Cassette Transporter, Subfamily B, Member 1 -- Genetics ; Antibiotics, Antineoplastic -- Pharmacology ; Doxorubicin -- Pharmacology ; Drug Resistance, Multiple -- Genetics ; Drug Resistance, Neoplasm -- Genetics ; Gene Expression Regulation, Neoplastic -- Drug Effects ; Morphinans -- Pharmacology
descriptionChemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that sinomenine can enhance the absorption of various P-gp substrates. In the present study, we investigated the effect of sinomenine on the chemoresistance in colon cancer cells and explored the underlying mechanism. We developed multidrug-resistant Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1 genes as well as activation of the NF-κB signal pathway in MDR-Caco-2 cells. Importantly, we found that sinomenine enhances the sensitivity of MDR-Caco-2 cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through inhibition of the NF-κB signaling pathway. These findings provide a new potential strategy for the reversal of P-gp-mediated anticancer drug resistance....
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titleSinomenine sensitizes multidrug-resistant colon cancer cells (Caco-2) to doxorubicin by downregulation of MDR-1 expression
descriptionChemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that sinomenine can enhance the absorption of various P-gp substrates. In the present study, we investigated the effect of sinomenine on the chemoresistance in colon cancer cells and explored the underlying mechanism. We developed multidrug-resistant Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1 genes as well as activation of the NF-κB signal pathway in MDR-Caco-2 cells. Importantly, we found that sinomenine enhances the sensitivity of MDR-Caco-2 cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through inhibition of the NF-κB signaling pathway. These findings provide a new potential strategy for the reversal of P-gp-mediated anticancer drug resistance....
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titleSinomenine sensitizes multidrug-resistant colon cancer cells (Caco-2) to doxorubicin by downregulation of MDR-1 expression
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abstractChemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that sinomenine can enhance the absorption of various P-gp substrates. In the present study, we investigated the effect of sinomenine on the chemoresistance in colon cancer cells and explored the underlying mechanism. We developed multidrug-resistant Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1 genes as well as activation of the NF-κB signal pathway in MDR-Caco-2 cells. Importantly, we found that sinomenine enhances the sensitivity of MDR-Caco-2 cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through inhibition of the NF-κB signaling pathway. These findings provide a new potential strategy for the reversal of P-gp-mediated anticancer drug resistance....
doi10.1371/journal.pone.0098560
pmid24901713