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新型膳食补充剂 Coltect 单独及与 5-氨基水杨酸联合应用对二甲基肼诱导的大鼠结肠癌的化学预防作用。

Chemopreventive effects of Coltect, a novel dietary supplement, alone and in combination with 5-aminosalicylic acid in 1,2-dimethylhydrazine-induced colon cancer in rats.

机构信息

Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

出版信息

Therap Adv Gastroenterol. 2010 Sep;3(5):281-9. doi: 10.1177/1756283X10379258.

Abstract

OBJECTIVES

Coltect is a novel dietary supplement containing curcumin, green tea and selenomethionine. Previous reports have suggested that these agents can prevent colorectal cancer (CRC). The present study examined the chemopreventive effect of Coltect alone or combined with 5-aminosalicylic acid (5-ASA) using the 1,2-dimethylhydrazine (DMH) model in rats.

METHODS

The effect of Coltect was examined on HT-29 CRC cells by growth inhibition assay. Apoptosis was determined by annexin V-FITC/PI staining. Male rats were injected with DMH in vivo and treated with Coltect 150 mg/kg, 5-ASA 50 mg/kg or their combination, by oral gavage. Aberrant crypt foci (ACF) were identified by methylene blue staining.

RESULTS

HT-29 cells exhibited a dose-dependent response to Coltect. Part of the growth inhibition can be explained by the induction of mild-moderate apoptosis in cancer cells (28%) compared with the untreated cells (10%). In the in vivo model, the average number of ACF was divided into small (1-3 crypts) or large (≥4 crypts). The Coltect compound reduced the number of small and large ACF similarly to 5-ASA (40% reduction). This reduction was amplified by combining the two agents (70% reduction).

CONCLUSION

Coltect inhibits the growth of colon cancer cells, induces apoptosis and inhibits ACF development. Furthermore, it augments the growth inhibitory effect of 5-ASA in vivo. This may be clinically important since this safe dietary supplement-drug combination can be administered as a chemopreventive regimen for the treatment of CRC.

摘要

目的

Coltect 是一种新型膳食补充剂,含有姜黄素、绿茶和硒代蛋氨酸。先前的报告表明,这些药物可以预防结直肠癌(CRC)。本研究使用 1,2-二甲基肼(DMH)模型在大鼠中检查了 Coltect 单独或与 5-氨基水杨酸(5-ASA)联合使用的化学预防作用。

方法

通过生长抑制试验检查 Coltect 对 HT-29 CRC 细胞的作用。通过 Annexin V-FITC/PI 染色测定细胞凋亡。雄性大鼠体内注射 DMH,并通过口服灌胃给予 Coltect 150mg/kg、5-ASA 50mg/kg 或它们的组合。通过亚甲蓝染色鉴定异常隐窝病灶(ACF)。

结果

HT-29 细胞对 Coltect 表现出剂量依赖性反应。与未经处理的细胞(10%)相比,部分生长抑制可归因于癌细胞中诱导的轻度中度凋亡(28%)。在体内模型中,ACF 的平均数量分为小(1-3 个隐窝)或大(≥4 个隐窝)。Coltect 化合物降低小和大 ACF 的数量与 5-ASA 相似(减少 40%)。将两种药物联合使用可放大这种减少(减少 70%)。

结论

Coltect 抑制结肠癌细胞的生长,诱导细胞凋亡并抑制 ACF 的发展。此外,它增强了 5-ASA 在体内的生长抑制作用。这在临床上可能很重要,因为这种安全的膳食补充剂-药物组合可以作为 CRC 的化学预防方案进行管理。

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