論文 - 詳細
| RRC ID | 44796 |
|---|---|
| 著者 | Ogawa F, Amano H, Ito Y, Matsui Y, Hosono K, Kitasato H, Satoh Y, Majima M. |
| タイトル | Aspirin reduces lung cancer metastasis to regional lymph nodes. |
| ジャーナル | Biomed Pharmacother |
| 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. |
| 巻・号 | 68(1) |
| ページ | 79-86 |
| 公開日 | 2014-2-1 |
| DOI | 10.1016/j.biopha.2013.11.006 |
| PII | S0753-3322(13)00135-2 |
| PMID | 24331369 |
| MeSH | Animals Aspirin / pharmacology* Carcinoma, Lewis Lung / drug therapy* Carcinoma, Lewis Lung / pathology Cyclooxygenase Inhibitors / pharmacology* Green Fluorescent Proteins Lung Neoplasms / drug therapy* Lung Neoplasms / pathology Lymphatic Metastasis / prevention & control Male Mediastinum Mice Mice, Inbred C57BL Neoplasm Transplantation Survival Rate Time Factors |
| IF | 4.545 |
| 引用数 | 20 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL PHARMACOLOGY & PHARMACY |
| リソース情報 | |
| ヒト・動物細胞 | LLC(RCB0558) |