title: Simvastatin prevents proliferation and bone metastases of lung adenocarcinoma in vitro and in vivo.
abstract: OBJECTIVE
  To explore the mechanism about how HMG-CoA reductase (HMGR) inhibitor inhibit proliferation and bone metastases of lung adenocarcinoma in vitro and in vivo.
  
  
  METHODS
  The HMGR inhibitor simvastatin, human lung cancer cell line A549 and Balb/c nude mouse were used in this study. The mice were randomly divided into 2 groups: control group (0.9% NaCl solution, i.v.) and simvastatin group (5mg/kg simvastatin, i.v.). A scratch assay using A549 cell monolayer was also tested. An invasion assay using collagen-coated membrane in trans-wells was applied to evaluate the effect of simvastatin on the metastatic potential of A549 cells in vitro. The expressions of CD44, PUMA, P53, MMP2 and MMP9 were determined by real-time PCR and western blotting; the phosphorylation status of MAPK/ERK signaling parthway was investigated by western blot. .
  
  
  RESULTS
  Compared with the control group, the migration of A549 cells in simvastatin-treated group was markedly inhibited (p ≤ 0.01). Untreated A549 cells showed marked invasion, while simvastatin significantly inhibited the invasion of tumor cells (p ≤ 0.001). Incubation of A549 cells with simvastatin significantly reduced the levels of CD44, MMP2 and MMP9 (p <0.01), while significantly increased p53 (p < 0.01). Simvastatin significantly inhibits tumor growth and bone metastasis in lung cancer xenograft mouse model, simvastatin can inhibit the kinase phosphorylation inMAPK/ERK signaling parthway.
  
  
  CONCLUSIONS
  The HMGR inhibitor simvastatin prevents proliferation and osteolytic bone metastases of lung adenocarcinoma cells in vitro and vivo. Its mechanism may be associated with regulation of CD44, P53, MMP family and inactivation of MAPK/ERK signaling parthway.
authors: Department of Orthopedic and Trauma Surgery, Shandong University, Jinan, China.
authors: H
authors: H
authors: Liu
authors: Z
authors: Z
authors: Wang
authors: Y
authors: Y
authors: Li
authors: W
authors: W
authors: Li
authors: Y
authors: Y
authors: Chen
mesh_terms: D000214:Acyl Coenzyme A / Q000037:antagonists & inhibitors; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D000214:Acyl Coenzyme A; D014408:Biomarkers, Tumor; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D019821:Simvastatin