Han Yi-Li, He Da-Lin, Luo Yong, Cheng He-Peng, Zhu Guang-Feng
Department of Urology, First Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, China.
Zhonghua Nan Ke Xue. 2008 May;14(5):439-44.
To observe the influence of hypoxia-inducible factor 1 alpha (HIF-1alpha) on angiogenesis in prostate carcinoma in vivo and to investigate its molecular mechanism.
LNCaP/HIF-1alpha and LNCaP cells were cultured, the level of PSA in the supernatant of the culture medium detected by ELISA assay before and after the transfection, and the cellular cycle measured by flow cytometry. Nude mouse models of subcutaneous tumor were established with LNCaP/HIF-1alpha and LNCaP cells, the tumor growth observed, and tumor specimens collected for immunohistochemical staining.
Compared with the LNCaP cells, LNCaP/HIF-1alpha cells showed an obviously decreased PSA level (t = 8.243, P < 0.05) and enhanced proliferous activity. The tumorigenesis rate increased and the tumorigenesis time advanced in the LNCaP/HIF-1alpha group of the nude mice. Immunohistochemistry displayed higher expressions of VEGF, iNOS and Ang-2 in the LNCaP/HIF-1alpha than in the LNCaP group.
The over-expression of HIF-1alpha can up-regulate VEGF and iNOS involved in angiogenesis in vivo and contribute to the invasive potency of LNCaP cells. HIF-1alpha may have no influence on Ang-2 either in vitro or in vivo, while the expression of Ang-2 is regulated by other factors in vivo.
观察缺氧诱导因子1α（HIF-1α）对前列腺癌体内血管生成的影响，并探讨其分子机制。
培养LNCaP/HIF-1α和LNCaP细胞，转染前后采用ELISA法检测培养基上清液中PSA水平，采用流式细胞术检测细胞周期。用LNCaP/HIF-1α和LNCaP细胞建立皮下肿瘤裸鼠模型，观察肿瘤生长情况，并收集肿瘤标本进行免疫组织化学染色。
与LNCaP细胞相比，LNCaP/HIF-1α细胞PSA水平明显降低（t = 8.243，P < 0.05），增殖活性增强。裸鼠LNCaP/HIF-1α组肿瘤发生率增加，肿瘤发生时间提前。免疫组织化学显示，LNCaP/HIF-1α组VEGF、iNOS和Ang-2的表达高于LNCaP组。
HIF-1α的过表达可上调体内血管生成相关的VEGF和iNOS，促进LNCaP细胞的侵袭能力。HIF-1α在体外和体内对Ang-2可能均无影响，而Ang-2的表达在体内受其他因素调控。
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