title: Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway.
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.
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences; Department of Epidemiology, First Affiliated Hospital.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Coloproctology, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Wanle
authors.initials: W
authors.lastname: Hu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences; Department of Epidemiology, First Affiliated Hospital.
authors.forename: Encheng
authors.initials: E
authors.lastname: Bai
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences.
authors.forename: Hailun
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences.
authors.forename: Jianzhang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, First Affiliated Hospital.
authors.forename: Rong
authors.initials: R
authors.lastname: Jin
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences.
authors.forename: Chengguang
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
keywords: 5-FU; NFκB; curcumin; drug resistance; gastric cancer