Intact nitric oxide synthase II gene is required for interferon-beta-mediated suppression of growth and metastasis of pancreatic adenocarcinoma.

Journal Article

Previous studies have shown that enforced expression of IFN-beta suppressed tumor growth and metastasis. In this report, we determined whether the induction of nitric oxide synthase II (NOS II) gene is required for IFN-beta-mediated antitumor activity using syngeneic mice with intact (NOS II+/+) or genetically disrupted (NOS II-/-) NOS II gene. PANC02-H7 highly metastatic murine pancreatic adenocarcinoma cells were transfected with an IFN-beta expression vector or a control pcDNA3 vector. The parental PANC02-H7, control vector-transfected, and IFN-beta-transfected cells were orthotopically implanted into the pancreas of syngeneic NOS II+/+ and NOS II-/- C57BL/6J mice. In NOS II+/+ C57BL/ 6J, both parental and control vector-transfected cells grew progressively in pancreas and produced numerous liver metastases and a large amount of malignant ascites, whereas IFN-beta-secreting cells did not. In NOS II-/- C57BL/6J mice, however, IFN-beta-secreting cells grew much more aggressively. Higher NO induction was detected in NOS II+/+ mice that received injections with IFN-beta-secreting cells than with the control cells, but it was not detected in NOS II-/- mice. These data suggested that IFN-beta secreted from tumor cells stimulates NO production by host cells and suppresses tumor growth and metastasis.

Duke Authors

Cited Authors

  • Wang, B; Xiong, Q; Shi, Q; Le, X; Abbruzzese, JL; Xie, K

Published Date

  • January 2001

Published In

Volume / Issue

  • 61 / 1

Start / End Page

  • 71 - 75

PubMed ID

  • 11196200

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

International Standard Serial Number (ISSN)

  • 0008-5472

Language

  • eng