title: Roxithromycin reduces the viability of cultured airway smooth muscle cells from a rat model of asthma.
abstract: OBJECTIVE
  The purpose of this study was to investigate the effect of roxithromycin on apoptosis of airway smooth muscle cells (ASMCs) from a rat model of asthma and uncover signaling pathway underlying the cytotoxicity of roxithromycin.
  
  
  METHODS
  ASMCs were isolated from a rat model of asthma and treated with or without roxithromycin for 48 h before parameter detection. Cell viability was assessed by WST-8 assay and flow cytometry after Annexin V/PI double staining. Changes in the mitochondrial membrane potential (ΔΨm) were measured by flow cytometry using JC-1. Cytochrome C (Cyt c), cleaved Caspase-9/3 and P27 were evaluated by Western Blot.
  
  
  RESULTS
  Incubation with roxithromycin reduced ASMCs proliferation and enhanced apoptosis in a dose-dependent manner. Flow cytometry revealed a loss of ΔΨm and Western Blot displayed Caspase-9/3 activation as well as Cyt c release from mitochondria to the the cytosol after the treatment of roxithromycin. In addition, P27 were more strongly expressed in AMSCs treated with roxithromycin compared with the control group.
  
  
  CONCLUSIONS
  Roxithromycin induced apoptosis of ASMCs derived from a rat model of asthma in a dose-dependent manner via a caspase-3- and caspase-9-dependent mitochondrial pathway, involving the up-regulation of P27.
authors.affiliation: Department of Respiratory, the Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China. yuanrongdai@126.com.
authors.forename: Y-R
authors.initials: YR
authors.lastname: Dai
authors.forename: H-Y
authors.initials: HY
authors.lastname: Wu
authors.forename: L-Q
authors.initials: LQ
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Yin
authors.forename: S-S
authors.initials: SS
authors.lastname: Yan
authors.forename: W-X
authors.initials: WX
authors.lastname: Zeng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015575:Roxithromycin / Q000627:therapeutic use / Q000633:toxicity*
chemical_list: D015575:Roxithromycin