Plasminogen activator inhibitor 1 RNAi suppresses gastric cancer metastasis in vivo
Plasminogen activator inhibitor 1 RNAi suppresses gastric cancer metastasis in vivo
复制标题
DOI：
10.1111/j.1349-7006.2011.02155.x
复制
发表时间：
2012-02-01
期刊：
影响因子：
5.7
通讯作者：
Roberts, John D.
中科院分区：
文献类型：
--
作者：
Nishioka, Nobuaki;Matsuoka, Tasuku;Roberts, John D.
癌症转移仍然是癌症患者疼痛、痛苦和死亡的主要原因，即使是最新的治疗策略在预防或抑制转移方面也不是非常成功。在大多数硬化性胃癌（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术后也会发生复发，最常见的是腹膜转移的形式。鉴于弥漫型胃癌的发生率一直在增加，开发新的策略来对抗这种疾病的转移是至关重要的。纤溶酶原激活物抑制剂-1（派-1）是肿瘤进展的关键因子，因此，派-1 RNAi可能是一种有效的抗肿瘤转移的治疗方法。在本研究中，我们使用RNAi技术来降低派-1在胃癌转移的体内模型系统中的表达。体外质粒转染和腺病毒感染作为将特异性派-1 RNAi载体掺入人胃癌细胞的机制进行了测试。这两种方法都显着降低了小鼠模型中腹膜肿瘤的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了一种新的有效策略。（Cancer Sci 2012; 103：228232）
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: 228232)