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The experimental study of specific COX-2 inhibitors applied to non-surgical therapy of postoperative recurrences and distant metastasis of lung cancer.

特异性COX-2抑制剂应用于肺癌术后复发及远处转移非手术治疗的实验研究

基本信息

批准号：
11670160
负责人：
KOZAKI Ken-ichi
金额：
$ 1.98万
依托单位：
Aichi Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

Although a large number of studies have been conducted, yielding considerable information about the metastatic processes, very little is known about how cancer cells propagate distantmetastasis and about target molecules applied to non-surgical therapy of postoperative recurrences and distant metastasis. Identification of molecules with a crucial role in the distant spread of lungcancer cells has been hampered by scarcity of an appropriate experimental model system. We recently reported the successful establishment of a highly metastatic human lung cancer cell line, NCI-H460-LNM35 (hereafter referred to as LNM35), which is capable of spontaneous metastases not only via hematogenous but also lymphogenous routes with a 100% incidence. In the present study, we found that cyclooxygenase 2 (COX-2) expression llevels correlated well with the capabilities of LNM35 for not only in vitro motility and invasion but also in vivo metastasis, while specific COX-2 inhibitors were shown for the first time to reduce lung cancer metastasis in vivo. The present study thus strengthens our previously stated concept that COX-2 may play a role in the metastatic processes of lung cancers and suggests the potentially clinical usefulness of specific COX-2 inhibitors for the treatment of lung cancer cases. Further, expression-profiling analysisrevealed that, while COX-2 itself is known to be inducible in inflammation, up-regulation of various proinflammatory cytokines and angiogenic chemotactic chemokines was present in LNM35. This suggest that lung cancer cells may mimic inflammatory cells in the process of metastasis.

虽然已经进行了大量的研究，产生了相当多的信息转移的过程中，很少有人知道癌细胞如何传播distantmetastases和有关的目标分子应用于非手术治疗术后复发和远处转移。由于缺乏合适的实验模型系统，对肺癌细胞远距离扩散中起关键作用的分子的鉴定一直受到阻碍。我们最近报道了一个成功建立的高转移性人肺癌细胞系NCI-H460-LNM 35（以下简称LNM 35），该细胞系不仅能够通过血液途径而且能够通过淋巴途径自发转移，发生率为100%。在本研究中，我们发现环加氧酶2（考克斯-2）表达水平与LNM 35的体外运动和侵袭能力以及体内转移能力密切相关，而特异性的考克斯-2抑制剂首次被证明可以减少肺癌体内转移。因此，本研究加强了我们以前提出的概念，考克斯-2可能在肺癌的转移过程中发挥作用，并建议潜在的临床实用性的具体考克斯-2抑制剂治疗肺癌病例。此外，表达谱分析显示，虽然已知考克斯-2本身在炎症中是可诱导的，但LNM 35中存在多种促炎细胞因子和血管生成趋化因子的上调。这表明肺癌细胞在转移过程中可能模拟炎性细胞。