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Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway
Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for gastric cancer (GC). However, the occurrence of resistance to 5-FU treatment poses a major problem for its clinical efficacy. In this study, we found that the NFκB-signaling pathway can mediate 5-FU resistance in GC cells. We d...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147405/ https://www.ncbi.nlm.nih.gov/pubmed/27980427 http://dx.doi.org/10.2147/OTT.S118272 |
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author | Kang, Yanting Hu, Wanle Bai, Encheng Zheng, Hailun Liu, Zhiguo Wu, Jianzhang Jin, Rong Zhao, Chengguang Liang, Guang |
author_facet | Kang, Yanting Hu, Wanle Bai, Encheng Zheng, Hailun Liu, Zhiguo Wu, Jianzhang Jin, Rong Zhao, Chengguang Liang, Guang |
author_sort | Kang, Yanting |
collection | PubMed |
description | Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for gastric cancer (GC). However, the occurrence of resistance to 5-FU treatment poses a major problem for its clinical efficacy. In this study, we found that the NFκB-signaling pathway can mediate 5-FU resistance in GC cells. We developed a 5-FU-resistant GC cell line named SGCR/5-FU and found that the 5-FU-induced resistance increased cytosolic IκBα degradation and promoted NFκB nuclear translocation in GC cells. These findings were further confirmed by the activation of the NFκB survival-signaling pathway in clinical specimens. Curcumin, a natural compound, can reverse 5-FU resistance and inhibits proliferation in GC cells by downregulating the NFκB-signaling pathway. Moreover, it can also decrease the expression level of TNFα messenger RNA. Flow cytometry and Western blot analysis results showed that the combination of curcumin and 5-FU caused synergistic inhibition of growth and induction of potent apoptosis in the resistant cancer cell lines in vitro. In conclusion, our results demonstrate that the combination of 5-FU and curcumin could be further developed as a potential therapy for human GC. |
format | Online Article Text |
id | pubmed-5147405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-51474052016-12-15 Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway Kang, Yanting Hu, Wanle Bai, Encheng Zheng, Hailun Liu, Zhiguo Wu, Jianzhang Jin, Rong Zhao, Chengguang Liang, Guang Onco Targets Ther Original Research Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for gastric cancer (GC). However, the occurrence of resistance to 5-FU treatment poses a major problem for its clinical efficacy. In this study, we found that the NFκB-signaling pathway can mediate 5-FU resistance in GC cells. We developed a 5-FU-resistant GC cell line named SGCR/5-FU and found that the 5-FU-induced resistance increased cytosolic IκBα degradation and promoted NFκB nuclear translocation in GC cells. These findings were further confirmed by the activation of the NFκB survival-signaling pathway in clinical specimens. Curcumin, a natural compound, can reverse 5-FU resistance and inhibits proliferation in GC cells by downregulating the NFκB-signaling pathway. Moreover, it can also decrease the expression level of TNFα messenger RNA. Flow cytometry and Western blot analysis results showed that the combination of curcumin and 5-FU caused synergistic inhibition of growth and induction of potent apoptosis in the resistant cancer cell lines in vitro. In conclusion, our results demonstrate that the combination of 5-FU and curcumin could be further developed as a potential therapy for human GC. Dove Medical Press 2016-12-05 /pmc/articles/PMC5147405/ /pubmed/27980427 http://dx.doi.org/10.2147/OTT.S118272 Text en © 2016 Kang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Kang, Yanting Hu, Wanle Bai, Encheng Zheng, Hailun Liu, Zhiguo Wu, Jianzhang Jin, Rong Zhao, Chengguang Liang, Guang Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway |
title | Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway |
title_full | Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway |
title_fullStr | Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway |
title_full_unstemmed | Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway |
title_short | Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway |
title_sort | curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the nfκb survival-signaling pathway |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147405/ https://www.ncbi.nlm.nih.gov/pubmed/27980427 http://dx.doi.org/10.2147/OTT.S118272 |
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