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Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway

Authors Kang Y, Hu W, Bai E, Zheng H, Liu Z, Wu J, Jin R, Zhao C, Liang G

Received 27 July 2016

Accepted for publication 10 November 2016

Published 5 December 2016 Volume 2016:9 Pages 7373—7384

DOI https://doi.org/10.2147/OTT.S118272

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Norbert Ajeawung

Peer reviewer comments 4

Editor who approved publication: Prof. Dr. Geoffrey Pietersz

Yanting Kang,1,2,* Wanle Hu,3,* Encheng Bai,1,2 Hailun Zheng,1 Zhiguo Liu,1 Jianzhang Wu,1 Rong Jin,2 Chengguang Zhao,1 Guang Liang1

1Chemical Biology Research Center, School of Pharmaceutical Sciences, 2Department of Epidemiology, First Affiliated Hospital, 3Department of Coloproctology, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China

*These authors contributed equally to this work

Abstract: 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.

Keywords: 5-FU, curcumin, NFκB, drug resistance, gastric cancer

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