Urocortin's inhibition of tumor growth and angiogenesis in hepatocellular carcinoma via corticotrophin-releasing factor receptor 2.
Urocortin (UCN) functions via corticotrophin-releasing factor receptors (CRFRs), CRFR1 & 2. CRFR2 is reported to be a tonic suppressor of vascularization, implying its role in tumor angiogenesis. Here, it was found that UCN inhibited the growth of hepatocellular carcinoma (HCC) and reduced tumor microvessel density in nude mice. Hepatoma cells didn't express CRFRs whereas vessels expressed CRFRs, mainly CRFR2. In vitro three-dimensional culture assay showed UCN inhibited angiogenesis, this effect was abolished by CRFR2 antagonist, anti-sauvagine-30, demonstrating involvement of CRFR2. Furthermore, UCN inhibited the proliferation and promoted the apoptosis of endothelial cells and down-regulated VEGF expression in vivo via CRFR2.
Wang
Juejin
J
Department of Pharmacology, Nanjing Medical University, Nanjing, China.
Xu
Youhua
Y
Xu
Yinyan
Y
Zhu
Huayuan
H
Zhang
Rongjian
R
Zhang
Guoxin
G
Li
Shengnan
S
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000097:blood / Q000187:drug effects* / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects* / Q000502:physiology; D054832:Urocortins / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000097:blood; D023041:Xenograft Model Antitumor Assays
C101531:CRF receptor type 2; D009363:Neoplasm Proteins; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse