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长期口服白藜芦醇(3,5,3',4'-四羟基二苯乙烯)可减轻氧化偶氮甲烷加葡聚糖硫酸钠诱导的 C57BL/6J 小鼠结肠肿瘤生长。

Long-Term Oral Administration of Piceatannol (3,5,3',4'-Tetrahydroxystilbene) Attenuates Colon Tumor Growth Induced by Azoxymethane Plus Dextran Sulfate Sodium in C57BL/6J Mice.

机构信息

Department of Functional Biomedicine, Graduate School of Medicine, Ehime University, Toon City, Ehime, Japan.

出版信息

Nutr Cancer. 2022;74(6):2184-2195. doi: 10.1080/01635581.2021.1985532. Epub 2021 Oct 8.

Abstract

AIM

The effects of 3,5,3',4'-tetrahydroxystilbene (piceatannol) on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon cancer growth and changes in IL-1β, IL-6, tumor necrosis factor-α (cytokines), MCP-1, vascular endothelial growth factor, and PD-1 colon levels were investigated herein.

METHODS

AOM (10 mg/kg, ) on day 0 induced colorectal carcinogenesis. On day 3, mice were provided with water containing 1.5% (w/v) DSS for 3 day, and this 3-day drinking protocol was repeated twice. Piceatannol (5 and 12.5 mg/kg, twice daily) was orally administered to mice for 7-, 7-, 7-, and 6-day and then discontinued for 14-, 15-, and 16-day.

RESULTS

In mice administered piceatannol (12.5 mg/kg), the tumor number, tumor area, and Ki-67-positive cell numbers decreased by 30.1%, 57.2%, and 89.1%, respectively, colon MCP-1 and PD-1 levels showed reductions of 43.8% and 70.9%, respectively, and COX-2-positive cell numbers declined by 60.2%.

CONCLUSIONS

The inhibitory effects of piceatannol on AOM/DSS-induced colon tumor growth to be associated with reductions in colon MCP-1 and PD-1 levels through the downregulated expression of COX-2 in the tumor microenvironment.

摘要

目的

研究 3,5,3',4'-四羟基二苯乙烯(白藜芦醇)对氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)诱导的结肠癌生长的影响以及白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(细胞因子)、单核细胞趋化蛋白-1(MCP-1)、血管内皮生长因子和 PD-1 结肠水平的变化。

方法

AOM(10mg/kg,)在第 0 天诱导结直肠癌变。第 3 天,给予小鼠含有 1.5%(w/v)DSS 的水 3 天,该 3 天饮水方案重复两次。白藜芦醇(5 和 12.5mg/kg,每日两次)口服给予小鼠 7、7、7 和 6 天,然后停药 14、15 和 16 天。

结果

在给予白藜芦醇(12.5mg/kg)的小鼠中,肿瘤数量、肿瘤面积和 Ki-67 阳性细胞数分别减少了 30.1%、57.2%和 89.1%,结肠 MCP-1 和 PD-1 水平分别降低了 43.8%和 70.9%,COX-2 阳性细胞数减少了 60.2%。

结论

白藜芦醇对 AOM/DSS 诱导的结肠肿瘤生长的抑制作用可能与肿瘤微环境中 COX-2 表达下调导致结肠 MCP-1 和 PD-1 水平降低有关。

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