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.
Transl Lung Cancer Res. 2015 Feb;4(1):27-35. doi: 10.3978/j.issn.2218-6751.2014.11.03.
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.
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.
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.
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.
恶性胸腔积液（MPE）的存在表明非小细胞肺癌（NSCLC）患者预后不良。伊曲康唑已被确定为一种有效的内皮细胞增殖抑制剂，可抑制血管生成；然而，其在淋巴管生成抑制中的作用尚不清楚。本研究旨在探讨伊曲康唑治疗 MPE 的疗效及其抑制淋巴管生成的机制。
将 Lewis 肺癌（LLC）细胞注入小鼠胸腔，建立 MPE 小鼠模型，然后将小鼠随机分为三组。每组小鼠分别注射高剂量伊曲康唑（25mg/kg，H-ITCZ）、低剂量伊曲康唑（8mg/kg，L-ITCZ）或 50μL 羟丙基-β-环糊精（130mg/mL，H-β-C），每 3 天注射 4 次。用 1mL 注射器收集并测量小鼠胸腔积液。采用酶联免疫吸附试验（ELISA）检测 MPE 中血管内皮生长因子-C（VEGF-C）的表达水平，免疫组织化学（IHC）染色观察肿瘤组织中 VEGF-C 表达和淋巴管密度（LMVD）。
H-ITCZ 治疗组小鼠胸腔肿瘤灶数量、胸腔积液体积、LMVD 和肿瘤组织中 VEGF-C 表达水平均显著降低。
我们的研究结果表明，伊曲康唑可能通过抑制淋巴管生成在 MPE 小鼠中发挥重要作用，这表明伊曲康唑在治疗 MPE 中的有用性。
