Nitric oxide increases the invasion of pancreatic cancer cells via activation of the PI3K-AKT and RhoA pathways after carbon ion irradiation

FEBS Lett. 2014 Aug 25;588(17):3240-50. doi: 10.1016/j.febslet.2014.07.006. Epub 2014 Jul 11.

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.

Keywords: Invasion; Nitric oxide synthase; Phosphatidylinositol 3-kinase; Plasminogen activator; Rho; v-akt murine thymoma viral oncogene homolog 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA Damage / radiation effects
  • Enzyme Activation / radiation effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Heavy Ion Radiotherapy*
  • Humans
  • Neoplasm Invasiveness
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Pancreatic Neoplasms / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / radiation effects*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Nitric Oxide
  • Nitric Oxide Synthase
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • rhoA GTP-Binding Protein