Yunfen Wang1, Yanwen Yao1, Hongbin Liu1, Xingqun Ma1, Tangfeng Lv1, Dongmei Yuan1, Xinwu Xiao1, Jie Yin1, Yong Song1. 1. 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.
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.
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.
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