Open AccessPlasminogen activator inhibitor 1 RNAi suppresses gastric cancer metastasis in vivo
Author(s) -
Nishioka Nobuaki,
Matsuoka Tasuku,
Yashiro Masakazu,
Hirakawa Kosei,
Olden Kenneth,
Roberts John D.
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.02155.x
Subject(s) - metastasis , cancer , cancer research , plasminogen activator , medicine , cancer cell , in vivo , plasminogen activator inhibitor 1 , biology , microbiology and biotechnology
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. ( Cancer Sci 2012; 103: 228–232)