Abstract：
Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly-metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase-expressing (S18-1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI-related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5-8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR.
摘要：
远处转移是鼻咽癌（NPC）患者治疗失败的主要原因。在这项研究中,我们研究了乌司他丁（UTI）对NPC转移的影响及其潜在机制。用UTI处理高转移NPC细胞系S18和58F，对细胞增殖的影响，迁移,通过MTS和Transwell测定确定侵袭。将具有荧光素酶表达的S18细胞（S18-1C3）注射到裸鼠的左后足垫中，以建立从足垫到the淋巴结（LN）的自发转移模型。通过定量聚合酶链反应（qPCR）测量荧光素酶信使RNA（mRNA），并计算转移抑制率。UTI相关uPA的关键分子成员，uPAR,通过qPCR和免疫印迹检测JAT/STAT3信号通路。UTI抑制了S18和5-8F细胞的迁移和浸润，抑制了S18细胞在体内的转移，而不影响细胞增殖。uPAR表达在UTI治疗后24至48小时下降。UTI的抗转移作用部分归因于uPA和uPAR的抑制。UTI通过下调uPA和uPAR的表达部分抑制NPC转移。
