Effective tumor regression by anti-neovascular therapy in hypovascular orthotopic pancreatic tumor model.
Pancreatic cancer is one of the most serious cancers with poor therapeutic results and prognosis. In here, we proposed a novel treatment strategy of pancreatic cancer by injuring limited angiogenic vessels with liposome containing adriamycin. At first, we established an orthotopic tumor model, which has a hypovascular characteristic of pancreatic tumor. In this model, we obtained the enhanced therapeutic efficacy with liposome that modified by polyethylene glycol (PEG) and a peptide, Ala-Pro-Arg-Pro-Gly (APRPG), having an affinity to neovessels. Histochemical analysis suggested the degradation of angiogenic vessels after treatment with APRPG-PEG-liposomal adriamycin. In addition, we observed colocalization of fluorescence-labeled APRPG-PEG-liposome with angiogenic endothelial cells, although the biodistribution of (3)H-labeled liposome did not show the difference in the amount of accumulation between PEG-modified liposome and APRPG-PEG-modified liposome. These results suggested the availability of the anti-neovascular therapy against pancreatic cancer and supply a new sight indication on chemotherapeutics against pancreatic cancer.
Yonezawa
Sei
S
Department of Medical Biochemistry and COE Program in the 21st Century, University of Shizuoka School of Pharmaceutical Sciences, Yada, Suruga-ku, Shizuoka, Japan.
Asai
Tomohiro
T
Oku
Naoto
N
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000503:physiopathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D020533:Angiogenesis Inhibitors; D008081:Liposomes