阿司匹林可降低肺癌转移至局部淋巴结。

Aspirin reduces lung cancer metastasis to regional lymph nodes.

机构信息

Department of Pharmacology, Kitasato University School of Medicine, Kitasato1-15-1, Sagamihara, Kanagawa 252-0374, Japan; Department of Thoracic Surgery, Kitasato University School of Medicine, Kitasato1-15-1, Sagamihara, Kanagawa 252-0374, Japan.

Department of Pharmacology, Kitasato University School of Medicine, Kitasato1-15-1, Sagamihara, Kanagawa 252-0374, Japan.

出版信息

Biomed Pharmacother. 2014 Feb;68(1):79-86. doi: 10.1016/j.biopha.2013.11.006. Epub 2013 Nov 26.

DOI:10.1016/j.biopha.2013.11.006

PMID:24331369

Abstract

BACKGROUND

Lung cancer is the main cause of cancer-related death worldwide. The high mortality is probably attributable to early metastasis; however, the mechanism underlying metastasis to regional lymph nodes is still unknown. Cyclooxygenase (COX)-derived prostaglandin E2 (PGE2) induces tumor growth and metastasis and is associated with a poor prognosis. The present study investigated the effect of an authentic COX inhibitor, aspirin, on regional lymph node metastasis during the development of lung cancer in mice.

METHODS

An orthotopic intrapulmonary implantation model based on male C57BL/6 (6-8-weeks-old) mice was used. The lungs were injected with a solution containing Lewis lung carcinoma (LLC) cells overexpressing green fluorescent protein (GFP) and BD Matrigel(®). The effect of aspirin on mediastinal lymph node metastasis of LCC cells from the primary injection sites was then examined.

RESULTS

The implantation process took approximately 30 s per mouse and operative mortality was 10%. Single pulmonary nodules developed at the implanted site in 95% of animals, and regional mediastinal lymph node metastasis was observed at 14 days post-LLC-GFP cell injection in all mice that formed a primary lung tumor. The mean survival time of mice injected with LLC-GFP cells was 15±3 days (range, 12-22 days). Histopathological analysis revealed that no metastatic tumors developed in the regional mediastinal lymph nodes by Day 10-12 post-LLC-GFP cell injection and no metastasis to distant organs or distant lymph nodes was observed by Day 21 post-injection. Oral administration of aspirin (100 mg/kg, twice a day) after LLC-GFP cell injection inhibited metastasis to the regional lymph nodes, with no significant suppression of primary tumor growth in the lungs. Aspirin treatment led to a significant reduction in mortality (P<0.0001).

CONCLUSIONS

The present lymph node metastasis model is useful for evaluating the efficacy of agents that inhibit tumor metastasis to the regional lymph nodes. Aspirin reduced the metastasis of LLC-GFP cells injection to the regional lymph nodes, with a significant reduction in mortality. These findings suggested that COX inhibitors have potential for preventing lymph node metastasis.

摘要

背景

肺癌是全球癌症相关死亡的主要原因。高死亡率可能归因于早期转移；然而，区域淋巴结转移的机制仍不清楚。环氧化酶（COX）衍生的前列腺素 E2（PGE2）诱导肿瘤生长和转移，并与预后不良相关。本研究探讨了真实 COX 抑制剂阿司匹林对小鼠肺癌发展过程中区域淋巴结转移的影响。

方法

使用基于雄性 C57BL/6（6-8 周龄）小鼠的原位肺内植入模型。将含有过表达绿色荧光蛋白（GFP）和 BD Matrigel（®）的 Lewis 肺癌（LLC）细胞溶液注入肺部。然后检查阿司匹林对来自原发性注射部位的 LCC 细胞纵隔淋巴结转移的影响。

结果

每个小鼠的植入过程大约需要 30 秒，手术死亡率为 10%。95%的动物在植入部位形成单个肺结节，所有形成原发性肺癌的小鼠在 LLC-GFP 细胞注射后 14 天观察到区域纵隔淋巴结转移。注射 LLC-GFP 细胞的小鼠的平均存活时间为 15±3 天（范围，12-22 天）。组织病理学分析显示，在 LLC-GFP 细胞注射后第 10-12 天，区域纵隔淋巴结未发生转移性肿瘤，在注射后第 21 天未观察到远处器官或远处淋巴结转移。LLC-GFP 细胞注射后口服阿司匹林（100mg/kg，每天两次）抑制了区域淋巴结转移，对肺部原发性肿瘤生长无明显抑制作用。阿司匹林治疗显著降低了死亡率（P<0.0001）。