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.
Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.