title: Itraconazole can inhibit malignant pleural effusion by suppressing lymphangiogenesis in mice.
abstract: BACKGROUND
  The presence of malignant pleural effusion (MPE) indicates a poor prognosis in patients with non-small cell lung cancer (NSCLC). Itraconazole has been identified as a potent inhibitor of endothelial cell proliferation that suppresses angiogenesis; however, its role in the suppression of lymphangiogenesis is still unclear. The aim of this study was to investigate the efficacy of itraconazole for MPE and the mechanism of lymphangiogenesis suppression.
  
  
  METHODS
  Lewis lung carcinoma (LLC) cells were injected into the mouse pleural cavity to establish the MPE mouse model, followed by randomization of the mice into three groups. Each mice was injected with either a high dose of itraconazole (25 mg/kg, H-ITCZ), a low dose of itraconazole (8 mg/kg, L-ITCZ), or 50 μL of hydroxypropyl-β-cyclodextrin (130 mg/mL, H-β-C) into the pleural cavity four times every 3 days. The MPE of the mice was collected and measured with a 1 mL syringe. The vascular endothelial growth factor-C (VEGF-C) expression level in the MPE was detected by enzyme-linked immunosorbent assay (ELISA), while the VEGF-C expression and lymphatic micro vessel density (LMVD) in the tumor tissue was observed by immunohistochemistry (IHC) staining.
  
  
  RESULTS
  The number of pleural tumor foci, the volume of pleural effusion, the LMVD and the VEGF-C expression levels in the tumor tissue were significantly reduced in the H-ITCZ-treated group.
  
  
  CONCLUSIONS
  Our results revealed that itraconazole may play an important role in the MPE mice by suppressing lymphangiogenesis, which demonstrated the usefulness of itraconazole in the treatment of MPE.
authors: 1 Department of Respiratory Medicine, Jinling Hospital, Nanjing Clinical School of Southern Medical University, Nanjing 210002, China ; 2 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China ; 3 Department of Medical Oncology, 81 Hospital of PLA, Nanjing 210002, China.
authors: Yunfen
authors: Y
authors: Wang
authors: 1 Department of Respiratory Medicine, Jinling Hospital, Nanjing Clinical School of Southern Medical University, Nanjing 210002, China ; 2 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China ; 3 Department of Medical Oncology, 81 Hospital of PLA, Nanjing 210002, China.
authors: Yanwen
authors: Y
authors: Yao
authors: 1 Department of Respiratory Medicine, Jinling Hospital, Nanjing Clinical School of Southern Medical University, Nanjing 210002, China ; 2 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China ; 3 Department of Medical Oncology, 81 Hospital of PLA, Nanjing 210002, China.
authors: Hongbin
authors: H
authors: Liu
authors: 1 Department of Respiratory Medicine, Jinling Hospital, Nanjing Clinical School of Southern Medical University, Nanjing 210002, China ; 2 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China ; 3 Department of Medical Oncology, 81 Hospital of PLA, Nanjing 210002, China.
authors: Xingqun
authors: X
authors: Ma
authors: 1 Department of Respiratory Medicine, Jinling Hospital, Nanjing Clinical School of Southern Medical University, Nanjing 210002, China ; 2 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China ; 3 Department of Medical Oncology, 81 Hospital of PLA, Nanjing 210002, China.
authors: Tangfeng
authors: T
authors: Lv
authors: 1 Department of Respiratory Medicine, Jinling Hospital, Nanjing Clinical School of Southern Medical University, Nanjing 210002, China ; 2 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China ; 3 Department of Medical Oncology, 81 Hospital of PLA, Nanjing 210002, China.
authors: Dongmei
authors: D
authors: Yuan
authors: 1 Department of Respiratory Medicine, Jinling Hospital, Nanjing Clinical School of Southern Medical University, Nanjing 210002, China ; 2 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China ; 3 Department of Medical Oncology, 81 Hospital of PLA, Nanjing 210002, China.
authors: Xinwu
authors: X
authors: Xiao
authors: 1 Department of Respiratory Medicine, Jinling Hospital, Nanjing Clinical School of Southern Medical University, Nanjing 210002, China ; 2 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China ; 3 Department of Medical Oncology, 81 Hospital of PLA, Nanjing 210002, China.
authors: Jie
authors: J
authors: Yin
authors: 1 Department of Respiratory Medicine, Jinling Hospital, Nanjing Clinical School of Southern Medical University, Nanjing 210002, China ; 2 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China ; 3 Department of Medical Oncology, 81 Hospital of PLA, Nanjing 210002, China.
authors: Yong
authors: Y
authors: Song
keywords: Itraconazole; lymphangiogenesis; lymphatic micro vessel density (LMVD); malignant pleural effusion (MPE); vascular endothelial growth factor-C (VEGF-C)