title: Synergistic inhibitory effect of gemcitabine and angiotensin type-1 receptor blocker, losartan, on murine pancreatic tumor growth via anti-angiogenic activities.
abstract: Pancreatic cancer is one of the leading causes of cancer death, and represents a challenging chemotherapeutic problem. The crucial role of angiogenesis in tumor growth has been widely recognized, and several reports have revealed that the combination treatment of the conventional chemotherapeutic drugs and anti-angiogenic agents exerted synergistic anti-cancerous effects. It has been reported that the clinically used angiotensin type-1 receptor blocker (ARB) exerted potent anti-angiogenic activity. The aim of our current study was to examine the combination effect of gemcitabine (GEM), a widely used conventional chemotherapeutic drug against pancreas cancer, and losartan (Lo), an ARB, on murine pancreatic tumor growth, especially in conjunction with angiogenesis. When used individually, GEM and Lo at clinically comparable low doses moderately suppressed pancreatic tumor development. The combination treatment with GEM and Lo exerted a marked inhibitory effect as compared with single agent treatments even after the tumor was fully established. Neovascularization and the expression of the vascular endothelial growth factor (VEGF), a central angiogenic factor, in the tumor were both markedly suppressed in a magnitude similar to the inhibitory effects against the tumor growth. Since both agents are widely used in the clinical practice, the combination regimen of GEM and Lo may represent a potential new therapeutic strategy for pancreatic cancer in the future.
authors: Third Department of Internal Medicine, Nara Medical University, Nara 634-8522, Japan.
authors: Ryuichi
authors: R
authors: Noguchi
authors: Hitoshi
authors: H
authors: Yoshiji
authors: Yasuhide
authors: Y
authors: Ikenaka
authors: Tadashi
authors: T
authors: Namisaki
authors: Mitsuteru
authors: M
authors: Kitade
authors: Kosuke
authors: K
authors: Kaji
authors: Junichi
authors: J
authors: Yoshii
authors: Koji
authors: K
authors: Yanase
authors: Masaharu
authors: M
authors: Yamazaki
authors: Tatsuhiro
authors: T
authors: Tsujimoto
authors: Hideto
authors: H
authors: Kawaratani
authors: Hiroshi
authors: H
authors: Fukui
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004357:Drug Synergism; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000188:drug therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D000093542:Gemcitabine
chemical_list: D020533:Angiogenesis Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D019808:Losartan; D000093542:Gemcitabine