Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer, and thymidine phosphorylase (TP) is a regulator of angiogenesis. To investigate the biological activities of TP in ICC, we established human cholangiocarcinoma RBE cell lines overexpressing TP or silencing TP. Overexpression of TP enhanced viability, suppressed apoptosis and increased tube formation in human umbilical vein endothelial cells, while downregulation of TP reversed these effects. Moreover, an orthotopic xenograft mouse model of ICC was built to further explore TP's function in ICC in vivo. Histological analysis using H&E, TUNEL and Ki67 staining showed that TP promoted tumour growth and inhibited cell apoptosis. Immunostaining for CD31 revealed an elevation in microvessel density in the presence of TP. Besides, upregulation of TP increased the expression of vascular endothelial growth factor, basic fibroblast growth factor, interleukin‐8 and tumour necrosis factor alpha. In contrast, TP knockdown inhibited tumour growth, suppressed microvessel formation and decreased the expression of angiogenesis‐related proteins. Therefore, we suggest that TP promotes angiogenesis and tumour growth in ICC, which can be a potent therapeutic target for ICC treatment.

中文翻译：

---

胸苷磷酸化酶促进肝内胆管癌的血管生成和肿瘤生长。

肝内胆管癌（ICC）是第二常见的原发性肝癌，胸苷磷酸化酶（TP）是血管生成的调节剂。为了研究TP在ICC中的生物学活性，我们建立了人TP或TP沉默的人胆管癌RBE细胞系。TP的过表达增强了人脐静脉内皮细胞的活力，抑制了细胞凋亡并增加了管的形成，而TP的下调则逆转了这些作用。此外，建立了ICC的原位异种移植小鼠模型以进一步探索TP在ICC体内的功能。使用H＆E，TUNEL和Ki67染色的组织学分析表明TP促进肿瘤生长并抑制细胞凋亡。CD31的免疫染色显示在TP存在下微血管密度升高。除了，TP的上调增加了血管内皮生长因子，碱性成纤维细胞生长因子，白介素-8和肿瘤坏死因子α的表达。相反，TP抑制可抑制肿瘤生长，抑制微血管形成并降低血管生成相关蛋白的表达。因此，我们建议TP促进ICC中的血管生成和肿瘤生长，这可能是ICC治疗的有效治疗靶标。