2-Aminophenoxazine-3-one Prevents Pulmonary Metastasis of Mouse B16 Melanoma Cells in Mice
2-Aminophenoxazine-3-one Prevents Pulmonary Metastasis of Mouse B16 Melanoma Cells in Mice
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DOI：
10.1254/jphs.10023fp
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发表时间：
2010-09-01
影响因子：
3.5
通讯作者：
Tomoda, Akio
中科院分区：
文献类型：
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作者：
Hongo, Takayuki;Miyano-Kurosaki, Naoko;Tomoda, Akio
2-氨基吩恶嗪-3-酮（Phx-3）体外诱导小鼠黑色素瘤B16细胞凋亡，并上调Fas表达。接下来，在C56 BL/6小鼠中研究了Phx-3的抗转移作用。当将B16黑素瘤细胞注射到小鼠的尾静脉中时，在治疗后14天，在肺中指示细胞的显著转移。相反，当通过尾静脉向小鼠施用0.5mg/kg Phx-3时，与施用B16黑素瘤细胞同时施用一次或在施用B16黑素瘤细胞后每三天施用一次，转移的肺细胞的数量极大地减少。在注射细胞后第3天，在用单剂量的Phx-3的小鼠中表明转移的肺细胞的数量中度减少。然而，当以单剂量施用Phx-3时，在注射细胞后6或9天，转移的肺细胞的数量保持相同。目前的结果表明，小鼠B16黑色素瘤细胞转移到肺中的Phx-3，激活内在和外在的凋亡途径的小鼠给予显着抑制。本研究表明，Phx-3可能是一种潜在的抗转移剂以及抗癌剂。
2-Aminophenoxazine-3-one (Phx-3) induced cellular apoptosis in mouse melanoma B16 cells as detected by DNA laddering and upregulated Fas expression in the cells in vitro. Next, the anti-metastatic effects of Phx-3 were investigated in C56BL/6 mice. When B16 melanoma cells were injected into the tail veins of mice, significant metastasis of the cells was indicated in the lungs, 14 days after treatment. In contrast, when 0.5 mg/kg Phx-3 was administered to mice through the tail veins, once simultaneously with or every three days after the administration of B16 melanoma cells, the number of metastasized pulmonary cells was extremely reduced. Moderate reduction of the number of metastasized pulmonary cells was indicated in the mice with a single dose of Phx-3 on day 3 after injection of the cells. However, when Phx-3 was administered in a single dose, 6 or 9 days after the injection of the cells, the number of metastasized pulmonary cells remained the same. The present results indicate that the metastasis of mouse B16 melanoma cells to the lung was significantly inhibited in mice administered Phx-3, which activated the intrinsic and extrinsic apoptotic pathways. The present study suggests that Phx-3 might be a potential anti-metastatic agent as well as an anticancer agent.