Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Cancer Sci. 2012 Feb;103(2):228-32. doi: 10.1111/j.1349-7006.2011.02155.x. Epub 2012 Jan 9.
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.
癌症转移仍然是癌症患者疼痛、痛苦和死亡的主要原因，即使是最先进的治疗策略也未能在预防或抑制转移方面取得高度成功。在大多数硬癌（弥漫型胃癌中最具侵袭性的一种）患者中，即使在潜在的治愈性切除后也会发生复发，最常见的形式是腹膜转移。鉴于弥漫型胃癌的发生率不断增加，开发新的策略来对抗这种疾病的转移至关重要。纤溶酶原激活物抑制剂-1（PAI-1）是癌症进展的关键因素；因此，PAI-1 RNAi 可能是一种有效的癌症转移治疗方法。在本研究中，我们使用 RNAi 技术在胃癌转移的体内模型系统中降低 PAI-1 的表达。体外质粒转染和腺病毒感染被测试作为将特定的 PAI-1 RNAi 载体纳入人胃癌细胞的机制。这两种方法都显著减少了小鼠模型中的腹膜肿瘤生长和血性腹水的形成，表明这种方法可能为抑制癌症转移提供一种新的、有效的策略。
