Irradiation alters the invasive potential of PANC-1 cell line thorough NO and NOS-PI3K-AKT pathway activities in addition to the SerP activity

We have previously reported that Carbon ion (C-ion) irradiation suppresses the invasiveness of several pancreatic cancer cell lines, MIAPaCa-2, BxPC-3, and AsPC-1 cells, however, we also observed that C-ion irradiation enhanced invasion in PANC-1 cells, which occurred via the activation of serine proteases (SerP), plasmin, and uPA. Treatment of C-ion irradiated PANC-1 with SerP inhibitor and ROCK inhibitor resulted in reduced invasiveness, but only by 50%, suggesting that there are more factors that have a role in C-ion-irradiation-induced PANC-1 invasion. To study the molecular factors involved in irradiation-induced PANC-1 invasion, we used the Screening Committee of Anticancer Drugs (SCADS) compound library and found that nitric oxide synthase (NOS) inhibitors and phosphatidylinositol 3-kinases (PI3K) inhibitors were both effective in reducing PANC-1 invasion. Most invaded PANC-1 cells were nitric oxide (NO)-producing cells, and the NOS-PI3K-AKT pathway was activated in these cells. This effect could be abrogated by NOS inhibitor treatment, which also reduced invasion. The population of NO-producing cells was increased by C-ion irradiation, thereby enhancing C-ion-irradiation-induced PANC-1 invasion. These results suggested that irradiation alters the invasive potential through NO and NOS-PI3K-AKT pathway activities in addition to the SerP activity.Ninth AACR-Japanese Cancer Association Joint Conferenc