State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
Medical School, Pingdingshan University, Pingdingshan, China.
Drug Dev Res. 2023 Nov;84(7):1468-1481. doi: 10.1002/ddr.22098. Epub 2023 Aug 3.
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.
远处转移是鼻咽癌（NPC）患者治疗失败的主要原因。在本研究中，我们研究了尿胰蛋白酶抑制剂（UTI）对 NPC 转移的影响及其潜在机制。用 UTI 处理高转移性 NPC 细胞系 S18 和 58F，并通过 MTS 和 Transwell 分析测定细胞增殖、迁移和侵袭的影响。将表达荧光素酶的 S18 细胞（S18-1C3）注射到裸鼠左后足垫中，建立从足垫到腘淋巴结（LN）自发转移的模型。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。用 qPCR 和免疫印迹法检测 UTI 相关 uPA、uPAR 和 JAT/STAT3 信号通路的关键分子成员。UTI 抑制 S18 和 5-8F 细胞的迁移和浸润，并抑制 S18 细胞在体内的转移，而不影响细胞增殖。UTI 处理后 24 至 48 小时 uPAR 表达下降。UTI 的抗转移作用部分是由于 uPA 和 uPAR 的抑制。UTI 通过下调 uPA 和 uPAR 的表达部分抑制 NPC 转移。
