title: Chemoresistance to 5-fluorouracil induces epithelial-mesenchymal transition via up-regulation of Snail in MCF7 human breast cancer cells.
abstract: 5-Fluorouracil (5-FU) is commonly used to treat breast cancer; however, it becomes increasingly ineffective with tumor progression. Epithelial-to-mesenchymal transition (EMT) is a process whereby cells acquire morphologic and molecular alterations facilitating tumor metastasis and progression. Emerging evidence associates chemoresistance with acquisition of EMT in cancer. However, it is not clear whether this phenomenon is involved in acquired resistance to 5-FU. Using a previously established in vitro cell model of 5-fluorouracil-resistant MCF7 cells (MCF7/5-FU), we assessed the cellular morphology, molecular changes, migration and invasion consistent with EMT. We found that silencing of Snail by stable RNA interference reversed the EMT and greatly abolished invasion behavior of MCF7/5-FU cells. We also showed that inhibition of Snail increased the sensitivity of 5-FU-resistant cells to 5-FU. Our study provided a new insight into EMT-like phenotypic changes associated with 5-FU resistance in MCF7 cells. We believed that down-regulation of Snail could be a potential novel therapeutic approach to overcoming chemoresistance and preventing metastasis during 5-FU chemotherapy.
authors.affiliation: Cancer Research Institute, Xiang-Ya School of Medicine, Central South University, Changsha 410078, PR China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.forename: Meilin
authors.initials: M
authors.lastname: Feng
authors.forename: Guopei
authors.initials: G
authors.lastname: Zheng
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.forename: Xuedong
authors.initials: X
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Pen
authors.forename: Jiang
authors.initials: J
authors.lastname: Yin
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Yu
authors.forename: Zhimin
authors.initials: Z
authors.lastname: He
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D000964:Antimetabolites, Antineoplastic; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D005472:Fluorouracil