Sulindac, a non-steroidal anti-inflammatory drug, mediates breast cancer inhibition as an immune modulator.
Sulindac, a non-steroidal anti-inflammatory drug, mediates breast cancer inhibition as an immune modulator.
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舒林酸是一种非甾体抗炎药，作为免疫调节剂介导乳腺癌抑制
DOI：
10.1038/srep19534
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发表时间：
2016-01-18
影响因子：
4.6
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Yin T;Wang G;Ye T;Wang Y
获得性免疫与药物治疗的协同作用影响癌症的进展。尽管非类固醇抗炎药(NSAIDs)在预防癌症方面有着悠久的历史，但获得性免疫系统是否会影响这些药物的作用尚不清楚。在本研究中，我们揭示了舒林酸的一种新的免疫机制。我们的数据显示，舒林酸作为单一药物对4T1小鼠乳腺癌具有显著的疗效，并延长了荷瘤小鼠的生存时间。然而，在裸鼠中，舒林酸治疗无效。进一步的体内T细胞亚群耗竭实验表明，CD8+T细胞缺陷逆转了舒林酸的抗肿瘤作用。此外，舒林酸显著减少M2巨噬细胞募集、癌症相关炎症和肿瘤血管生成。我们的结果促进了我们对非甾体抗炎药机制的理解，更重要的是，这将为合理的药物设计或抗肿瘤免疫治疗提供洞察力。
The cooperation of adaptive immunity with pharmacologic therapy influences cancer progression. Though non-steroidal anti-inflammatory drugs (NSAIDs) have a long history of cancer prevention, it is unclear whether adaptive immune system affects the action of those drugs. In present study, we revealed a novel immunological mechanism of sulindac. Our data showed that sulindac had substantial efficacy as a single agent against 4T1 murine breast cancer and prolonged the survival of tumor-bearing mice. However, in the athymic nude mice, sulindac treatment was ineffective. Further in vivo T cell subsets depletion experiments showed that CD8+ T lymphocytes deficiency reversed the anti-tumor effect of sulindac. In addition, sulindac significantly reduced M2 macrophages recruitment, cancer-related inflammation and tumor angiogenesis. Our results advance our understanding of the mechanisms of NSAIDs, and more importantly, this will provide insight into rational drug design or antitumor immunotherapy.