title: Plasminogen activator inhibitor 1 RNAi suppresses gastric cancer metastasis in vivo.
abstract: Cancer metastasis remains the primary cause of pain, suffering, and death in cancer patients, and even the most current therapeutic strategies have not been highly successful in preventing or inhibiting metastasis. In most patients with scirrhous gastric cancer (one of the most aggressive of diffuse-type gastric cancer), recurrence occurs even after potentially curative resection, most frequently in the form of peritoneal metastasis. Given that the occurrence of diffuse-type gastric cancers has been increasing, the development of new strategies to combat metastasis of this disease is critically important. Plasminogen activator inhibitor-1 (PAI-1) is a critical factor in cancer progression; thus, PAI-1 RNAi may be an effective therapy against cancer metastasis. In the present study, we used an RNAi technique to reduce PAI-1 expression in an in vivo model system for gastric cancer metastasis. Ex vivo plasmid transfection and adenovirus infection were tested as mechanisms to incorporate specific PAI-1 RNAi vectors into human gastric carcinoma cells. Both approaches significantly decreased peritoneal tumor growth and the formation of bloody ascites in the mouse model, suggesting that this approach may provide a new, effective strategy for inhibiting cancer metastasis.
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Nishioka
authors.forename: Tasuku
authors.initials: T
authors.lastname: Matsuoka
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yashiro
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
authors.forename: Kenneth
authors.initials: K
authors.lastname: Olden
authors.forename: John D
authors.initials: JD
authors.lastname: Roberts
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014162:Transfection
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D034741:RNA, Small Interfering
references.citation: Nature. 2000 Mar 16;404(6775):293-6
references.pmid: 10749213
references.citation: Clin Cancer Res. 2003 Sep 15;9(11):4025-33
references.pmid: 14519623
references.citation: Arch Pathol Lab Med. 2004 Jul;128(7):765-70
references.pmid: 15214826
references.citation: Ann Oncol. 1991 Nov-Dec;2(10):751-4
references.pmid: 1801881
references.citation: Br J Cancer. 1995 Nov;72(5):1200-10
references.pmid: 7577468
references.citation: J Clin Oncol. 2001 Aug 1;19(15):3447-55
references.pmid: 11481349
references.citation: Int J Cell Biol. 2011;2011:562481
references.pmid: 21837240
references.citation: Clin Cancer Res. 2000 Aug;6(8):3056-61
references.pmid: 10955784
references.citation: Br J Cancer. 2011 Nov 22;105(11):1750-8
references.pmid: 22015554
references.citation: Br J Cancer. 2005 Apr 25;92(8):1398-405
references.pmid: 15846297
references.citation: Jpn J Cancer Res. 1999 Jul;90(7):747-52
references.pmid: 10470287
references.citation: Ann Oncol. 2004 Nov;15(11):1585-95
references.pmid: 15520058
references.citation: Anticancer Res. 1997 Jan-Feb;17(1A):313-6
references.pmid: 9066670
references.citation: Clin Exp Metastasis. 1996 Jan;14(1):43-54
references.pmid: 8521616
references.citation: Cancer. 1996 Apr 15;77(8 Suppl):1668-75
references.pmid: 8608560
references.citation: Eur J Cancer. 1994;30A(9):1263-9
references.pmid: 7999410
references.citation: Expert Opin Biol Ther. 2005 Jul;5(7):997-1005
references.pmid: 16018743
references.citation: Cell Mol Life Sci. 2000 Jan 20;57(1):25-40
references.pmid: 10949579
references.citation: Cancer Cell. 2002 Sep;2(3):243-7
references.pmid: 12242156
references.citation: Blood. 1997 Jul 1;90(1):204-8
references.pmid: 9207454
references.citation: Oncogene. 2004 Sep 9;23(41):6986-90
references.pmid: 15286708
references.citation: Expert Opin Investig Drugs. 2004 Jan;13(1):1-19
references.pmid: 14680449
references.citation: Gan To Kagaku Ryoho. 1988 Apr;15(4 Pt 2-2):1269-72
references.pmid: 2837987
references.citation: Semin Thromb Hemost. 1996;22(6):459-78
references.pmid: 9122711
references.citation: J Cell Biol. 1991 Oct;115(1):191-9
references.pmid: 1918136
references.citation: Nat Med. 1995 Jan;1(1):27-31
references.pmid: 7584949
references.citation: Exp Cell Res. 2004 Jun 10;296(2):151-62
references.pmid: 15149846
references.citation: J Clin Invest. 1995 Dec;96(6):2593-600
references.pmid: 8675623
references.citation: Dev Biol. 2003 Apr 1;256(1):187-93
references.pmid: 12654301
references.citation: Oncogene. 2004 Aug 12;23(36):6031-9
references.pmid: 15208655
references.citation: Thromb Haemost. 2004 Mar;91(3):438-49
references.pmid: 14983218