title: Effects of thapsigargin on the proliferation and survival of human rheumatoid arthritis synovial cells.
abstract: A series of experiments have been carried out to investigate the effects of different concentrations of thapsigargin (0, 0.001, 0.1, and 1 μM) on the proliferation and survival of human rheumatoid arthritis synovial cells (MH7A). The results showed that thapsigargin can block the cell proliferation in human rheumatoid arthritis synovial cells in a time- and dose-dependent manner. Results of Hoechst staining suggested that thapsigargin may induce cell apoptosis in MH7A cells in a time- and dose-dependent manner, and the percentages of cell death reached 44.6% at thapsigargin concentration of 1 μM treated for 4 days compared to the control. The protein and mRNA levels of cyclin D1 decreased gradually with the increasing of thapsigargin concentration and treatment times. Moreover, the protein levels of mTORC1 downstream indicators pS6K and p4EBP-1 were reduced by thapsigargin treatment at different concentrations and times, which should be responsible for the reduced cyclin D1 expressions. Our results revealed that thapsigargin may effectively impair the cell proliferation and survival of MH7A cells. The present findings will help to understand the molecular mechanism of fibroblast-like synoviocytes proliferations and suggest that thapsigargin is of potential for the clinical treatment of rheumatoid arthritis.
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, No. 23, Road Youzheng, Nangang District, Harbin, Heilongjiang 150001, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Immunology, Harbin Medical University, No. 157, Road Baojian, Nangang District, Harbin, Heilongjiang 150001, China.
authors.forename: Xiu-zhi
authors.initials: XZ
authors.lastname: Jia
authors.affiliation: Department of Gerontology, The First Affiliated Hospital of Harbin Medical University, No. 23, Road Youzheng, Harbin, Heilongjiang 150001, China.
authors.forename: Chun-jie
authors.initials: CJ
authors.lastname: Sui
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, No. 23, Road Youzheng, Nangang District, Harbin, Heilongjiang 150001, China.
authors.forename: Yan-ping
authors.initials: YP
authors.lastname: Zhao
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, No. 23, Road Youzheng, Nangang District, Harbin, Heilongjiang 150001, China.
authors.forename: Yi-fang
authors.initials: YF
authors.lastname: Mei
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, No. 23, Road Youzheng, Nangang District, Harbin, Heilongjiang 150001, China.
authors.forename: Yi-ning
authors.initials: YN
authors.lastname: Zheng
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, No. 23, Road Youzheng, Nangang District, Harbin, Heilongjiang 150001, China.
authors.forename: Zhi-yi
authors.initials: ZY
authors.lastname: Zhang
mesh_terms: D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D013582:Synovial Fluid / Q000166:cytology* / Q000187:drug effects*; D019284:Thapsigargin / Q000008:administration & dosage*
chemical_list: D019284:Thapsigargin