title: The bisphosphonate incadronate inhibits intraperitoneal dissemination             in an in vivo pancreatic cancer model.
abstract: Pancreatic cancer is characterized by intraperitoneal dissemination and often by large volumes of ascites. Aminobisphosphonates exhibit potent antitumor effects and are currently being tested against human solid tumors. Several aminobisphosphonates inhibit cancer cell migration by preventing the activation of Rho through inhibition of the mevalonate pathway. We evaluated the ability of an aminobisphosphonate, incadronate, to inhibit the growth of disseminated pancreatic cancer in vivo. We established an in vivo pancreatic cancer model with i.p. carcinomatosis in nude mice. Incadronate administration started from the day of tumor inoculation, and reduced tumor burden and ascites accumulation. Further, we evaluated the effect of incadronate on the inhibition of pancreatic cancer cell proliferation, migration and invasion in vitro. Incadronate induced growth inhibition and apoptotic death of pancreatic cancer cells. It also inhibited migration presumably by preventing the activation of Rho by lysophosphatidic acid. Thus, the in vivo antitumor effect may result from the inhibition of cancer cell proliferation and migration. The potent effects of incadronate in reducing tumor burden and ascites suggest that it will be of value in regimens for the treatment of pancreatic cancer.
authors.affiliation: Institute for Clinical Research, National Kyushu Cancer Center,                     Fukuoka 811-1395, Japan.
authors.forename: Soichi
authors.initials: S
authors.lastname: Takiguchi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nishino
authors.forename: Kazuko
authors.initials: K
authors.lastname: Inoue
authors.forename: Miyako
authors.initials: M
authors.lastname: Ikeda
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kataoka
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Matsusue
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Haruo
authors.initials: H
authors.lastname: Iguchi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; C071542:cimadronate; D054460:rho-Associated Kinases