[Over-expression of hypoxia-inducible factor 1 alpha increases angiogenesis of LNCaP cells in vivo].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Urology, First Hospital of Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, China. hanyili2000@yahoo.com.cn
Yi-Li
YL
Han
Da-Lin
DL
He
Yong
Y
Luo
He-Peng
HP
Cheng
Guang-Feng
GF
Zhu
D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D014162:Transfection; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D052247:Nitric Oxide Synthase Type II