title: Nitric oxide increases the invasion of pancreatic cancer cells via activation of the PI3K-AKT and RhoA pathways after carbon ion irradiation.
abstract: Previous studies have shown that serine proteases and Rho-associated kinase contribute to carbon ion radiation-enhanced invasion of the human pancreatic cancer cell line PANC-1. The results presented here show that nitric oxide synthase (NOS) also plays a critical role in this process. Irradiation of PANC-1 cells promoted invasion and production of nitric oxide (NO), which activated the PI3K-AKT signaling pathway, while independently activating RhoA. Inhibition of PI3K, Rho-associated kinase, and serine protease alone or in conjunction with NOS suppressed the radiation-enhanced invasion of PANC-1 cells, suggesting that they could serve as possible targets for the management of tumor metastasis.
authors.affiliation: Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Imadome
authors.affiliation: Research Center Hospital, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Endo
authors.affiliation: Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Shoji
authors.affiliation: Research Center Hospital, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263-8555, Japan. Electronic address: imait@nirs.go.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
mesh_terms: D045744:Cell Line, Tumor; D004249:DNA Damage / Q000528:radiation effects; D004789:Enzyme Activation / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D063193:Heavy Ion Radiotherapy; D006801:Humans; D009361:Neoplasm Invasiveness; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020742:rhoA GTP-Binding Protein
keywords: Invasion; Nitric oxide synthase; Phosphatidylinositol 3-kinase; Plasminogen activator; Rho; v-akt murine thymoma viral oncogene homolog 2