香豆素和7-羟基香豆素对小鼠肉瘤180的抗肿瘤及免疫调节作用。

Antitumor and immunomodulatory effect of coumarin and 7-hydroxycoumarin against Sarcoma 180 in mice.

作者信息

Stefanova Tsvetanka H, Nikolova Nadya J, Toshkova Reneta A, Neychev Hristo O

机构信息

Dept. of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev St., 1113 Sofia, Bulgaria.

出版信息

J Exp Ther Oncol. 2007;6(2):107-15.

PMID:17407969

Abstract

The antitumor effect of peroral treatment with coumarin and its main metabolite in humans 7-hydroxycoumarin (7-OHC) against Sarcoma 180 in mice was studied. Both agents inhibited tumor growth and increased survival time of tumor-bearing animals. The antitumor effect was better when coumarins were administered prior to tumor inoculation suggesting that the immunomodulatory potential of coumarins might exceed their well-known direct cytostatic activity. The additive effect of coumarins in combination with a suboptimal LPS dose in tumor growth inhibition was demonstrated. Coumarin treatment enhanced the macrophage migration activity in the presence and absence of LPS and increased nitric oxide release. In vitro, coumarins induced IL-12 in murine macrophages and additively increased the LPS-induced IL-12 release. These data indicate that the immunomodulatory activity of coumarins contributes to their direct cytostatic effect and demonstrate their potential to combine as immunostimulators with other antitumor agents.

摘要

研究了香豆素及其主要代谢产物7-羟基香豆素（7-OHC）经口给药对小鼠肉瘤180的抗肿瘤作用。两种药物均能抑制肿瘤生长并延长荷瘤动物的存活时间。在肿瘤接种前给予香豆素时，抗肿瘤效果更佳，这表明香豆素的免疫调节潜力可能超过其众所周知的直接细胞抑制活性。已证实香豆素与次优剂量的脂多糖（LPS）联合使用对肿瘤生长抑制具有相加作用。香豆素处理在有或无LPS的情况下均增强了巨噬细胞迁移活性，并增加了一氧化氮的释放。在体外，香豆素可诱导小鼠巨噬细胞产生白细胞介素-12（IL-12），并对LPS诱导的IL-12释放有相加作用。这些数据表明，香豆素的免疫调节活性有助于其直接的细胞抑制作用，并证明了它们作为免疫刺激剂与其他抗肿瘤药物联合使用的潜力。