title: Halofuginone inhibits TNF-α-induced the migration and proliferation of fibroblast-like synoviocytes from rheumatoid arthritis patients.
abstract: Fibroblast-like synoviocytes (FLSs) display an aggressive phenotype that is a critical factor in cartilage destruction in rheumatoid arthritis (RA). Increased FLS migration and proliferation are essential to the pathology of RA. Halofuginone has been found to inhibit cell migration and proliferation in cancer cells. However, whether halofuginone has a role in the treatment of RA FLSs is unclear. In this study, we found that halofuginone reduced migration, invasion, cell proliferation and MMPs expression in RA FLSs. In addition, we demonstrated that halofuginone inhibited reorganization of the actin cytoskeleton during cell migration. To gain insight into the molecular mechanisms, we evaluated the effect of halofuginone on the MAPK and AKT pathways. Our results indicated that halofuginone inhibited the activity of MAPK and AKT. Taken together, these results suggest that halofuginone may protect against joint destruction in RA by regulating synoviocyte migration, invasion and cell proliferation by inhibiting MAPK and AKT activation.
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangzhou, Guangdong, China.
authors.forename: Kefeng
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Mingcheng
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Maohua
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Hanshi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: lliuq@mail.sysu.edu.cn.
authors.forename: Liuqin
authors.initials: L
authors.lastname: Liang
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D052999:Quinazolinones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D000070918:Synoviocytes / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D010880:Piperidines; D052999:Quinazolinones; D014409:Tumor Necrosis Factor-alpha; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C010176:halofuginone