通过岩藻黄质抑制 AOM/DSS 小鼠肿瘤微环境的持续性可能与唾液甘氨酸有关。

Continuity of Tumor Microenvironmental Suppression in AOM/DSS Mice by Fucoxanthin May Be Able to Track With Salivary Glycine.

机构信息

School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Hokkaido, Japan

Advanced Research Promotion Center, Health Sciences University of Hokkaido, Hokkaido, Japan.

出版信息

In Vivo. 2020 Nov-Dec;34(6):3205-3215. doi: 10.21873/invivo.12156.

DOI:10.21873/invivo.12156

PMID:33144425

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7811669/

Abstract

BACKGROUND/AIM: Fucoxanthin (Fx) is a potent anticancer carotenoid, demonstrated by mouse cancer models. We recently showed the decrease of salivary glycine could represent an attenuation of tumor microenvironment (TME) formation in an azoxymethane/dextran sodium sulfate (AOM/DSS) colon cancer mouse model. However, it remains unclear whether the salivary glycine is an indicator for continuous TME suppression of Fx in the mice.

MATERIALS AND METHODS

In the present study, we time-dependently analyzed salivary metabolites in AOM/DSS mice, and investigated candidate markers to evaluate the continuous inhibition of colonic TME formation and carcinogenesis in the mice with and without Fx.

RESULTS

Fx attenuated the incidence and/or multiplicity of colonic lesions developed in AOM/DSS mice. The number of apoptosis-like cleaved caspase-3 cells was significantly increased, and colonic cancer stem cell-like CD44/EpCAM cells and cancer-associated fibroblast-like αSMA cells were significantly decreased in colon mucosal tissue by Fx administration. Salivary glycine at 4, 11 and 14 weeks after the final DSS exposure in the Fx-treated mice showed successful and consecutive decreases of 0.5-, 0.4- and 0.7-fold respectively compared to that of control mice.

CONCLUSION

Salivary glycine is a valuable indicator that could evaluate sustained efficacy of cancer chemopreventive effects of Fx in AOM/DSS mice.

摘要

背景/目的：褐藻黄素（Fx）是一种有效的抗癌类胡萝卜素，已在小鼠癌症模型中得到证实。我们最近发现唾液甘氨酸的减少可能代表了氧化偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）结肠癌小鼠模型中肿瘤微环境（TME）形成的减弱。然而，目前尚不清楚唾液甘氨酸是否是 Fx 在小鼠中持续抑制 TME 的指标。

材料和方法

在本研究中，我们对 AOM/DSS 小鼠的唾液代谢物进行了时间依赖性分析，并研究了候选标志物，以评估 Fx 对有和没有 Fx 的小鼠结肠 TME 形成和癌变的持续抑制作用。

结果

Fx 可减轻 AOM/DSS 小鼠结肠病变的发生率和/或多发性。Fx 处理组的结肠黏膜组织中，凋亡样裂解半胱氨酸蛋白酶-3 细胞数量显著增加，结肠癌症干细胞样 CD44/EpCAM 细胞和癌症相关成纤维样 αSMA 细胞显著减少。与对照组相比，Fx 处理组的小鼠在最后一次 DSS 暴露后的第 4、11 和 14 周，唾液甘氨酸分别成功连续下降了 0.5、0.4 和 0.7 倍。