title: [Effect of nitric oxide derived from endothelial nitric oxide synthase on tumor angiogenesis].
abstract: OBJECTIVE
  Studies have shown that nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS) is expressed widely in tumor tissues and regulates tumor angiogenesis. However, the results are controversial. This study was to investigate the effect of NO on tumor angiogenesis and its mechanism.
  
  
  METHODS
  C57BL/6 mice inoculated with Lewis lung cancer cells were randomly divided into three groups. Mice in the NO group were inoculated with lung cancer cells transfected with eNOS gene, mice in the L-NAME group with L-NAME, an eNOS antagonist, and mice in the control group with normal saline. Plasma concentration of NO and the number of endothelial progenitor cells (EPCs) in peripheral blood were detected . Tumor vessel density, CD133+ cells, and the expression of VEGF-VEGFR in tumor tissues were also measured.
  
  
  RESULTS
  Four weeks after inoculation of Lewis cells, tumor volume was significantly larger in control group [ (3022 +/- 401) mm(3)] than in the L-NAME group [ (1204 +/-97) ) mm(3)] and in the eNOS group [(1824 +/- 239) mm(3)] (P<0.01). eNOS protein and NO production increased significantly in Lewis lung cancer cells transfected with eNOS gene. But the number of CD133-positive cells and vessel density in tumors were significantly lower in the eNOS group than in the control group [(48+/-19) / HPF vs. ( 103 +/- 27)/ HPF, (19+/- 7) HPF vs. (31 +/- 9) HPF, P<0.05]. The number of EPCs in peripheral blood was not statistically different between each group. The levels of NO in blood and tumor tissue significantly decreased after the treatment of L-NAME, while the tumor vessel density reduced to 12+/- 5/ HPF (P<0.01, vs. the control group; P<0.05, vs the eNOS transfected group). The number of EPCs in blood and that of CD133-positive cells in tumor tissue were significantly smaller in the L-NAME group than in the control group (P<0.05).
  
  
  CONCLUSIONS
  No derived from eNOS inhibits angiogenesis and tumor growth, which may be due to its suppression on either the mobilization or homing of EPCs via VEGF binding to VEGFR.
authors.affiliation: Department of Medical Oncology,Sichuan Cancer Hospital, Chengdu, Sichuan 610041, People's Republic of China. meikai1973@yahoo.com.cn
authors.forename: Kai
authors.initials: K
authors.lastname: Mei
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Cai
authors.forename: Lei
authors.initials: L
authors.lastname: Du
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Chen
authors.forename: Shuang
authors.initials: S
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Xu-De
authors.initials: XD
authors.lastname: Yin
authors.forename: Zhi-Xuan
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Cheng-Ya
authors.initials: CY
authors.lastname: Zhou
authors.forename: Jing-Rui
authors.initials: JR
authors.lastname: Yu
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D009569:Nitric Oxide / Q000097:blood* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010957:Plasmids; D011897:Random Allocation; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D010455:Peptides; C000606024:Prom1 protein, mouse; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2; D019331:NG-Nitroarginine Methyl Ester