title: Recombinant human endostatin endostar suppresses angiogenesis and lymphangiogenesis of malignant pleural effusion in mice.
abstract: BACKGROUND
  Malignant pleural effusion (MPE) is a common complication of lung cancer. One widely used treatment for MPE is Endostar, a recombined humanized endostatin based treatment. However, the mechanism of this treatment is still unclear. The aim of this study was to investigate the effects of Endostar in mice with MPE.
  
  
  METHODS
  Lewis lung carcinoma (LLC) cell line expressing enhanced green fluorescent protein (EGFP) was injected into pleural cavity to establish MPE mice model. Mice were randomly divided into four groups. High dose of Endostar (30 mg/kg), low dose of Endostar (8 mg/kg), normal saline, or Bevacizumab (5 mg/kg) was respectively injected into pleural cavity three times with 3-day interval in each group. Transverse computed tomography (CT) was performed to observe pleural fluid formation 14 days after LLC cells injection. Mice were anesthetized and sacrificed 3 days after final administration. The volume of pleural effusion n was measured using 1 ml syringe. Micro blood vessel density (MVD), Lymphatic micro vessel density (LMVD), the expression level of vascular endothelial growth factor A (VEGF-A) and VEGF-C were observed by immunohistochemistry (IHC) staining.
  
  
  RESULTS
  The volume of pleural effusion as well as the number of pleural tumor foci, MVD and the expression of VEGF-A were significantly reduced in high dose of Endostar treat group. More importantly, LMVD and the expression of VEGF-C were markedly lower in treat group than those in the other three control groups.
  
  
  CONCLUSIONS
  Our work demonstrated that Endostar played an efficient anti-cancer role in MPE through its suppressive effect on angiogenesis and lymphangiogenesis, which provided a certain theoretical basis for the effectiveness of Endostar on the MPE treatment.
authors.affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xingqun
authors.initials: X
authors.lastname: Ma
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Yao
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yuan
authors.forename: Hongbing
authors.initials: H
authors.lastname: Liu
authors.forename: Shouju
authors.initials: S
authors.lastname: Wang
authors.forename: Changsheng
authors.initials: C
authors.lastname: Zhou
authors.forename: Yong
authors.initials: Y
authors.lastname: Song
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D043169:Endostatins / Q000494:pharmacology* / Q000627:therapeutic use; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D042583:Lymphangiogenesis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000517:prevention & control*; D016066:Pleural Effusion, Malignant / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D043169:Endostatins; D011994:Recombinant Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C522911:endostar protein