Fluoxetine induces preventive and complex effects against colon cancer development in epithelial and stromal areas in rats
Fluoxetine induces preventive and complex effects against colon cancer development in epithelial and stromal areas in rats
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DOI：
10.1016/j.toxlet.2011.04.024
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发表时间：
2011-07-28
影响因子：
3.5
通讯作者：
Garcia, Sergio B.
中科院分区：
文献类型：
--
作者：
Kannen, Vinicius;Marini, Tassiana;Garcia, Sergio B.
氟西汀（Fluoxetine，FIX）是一种常用的抗抑郁药。然而，其对肿瘤发生的影响仍然存在争议。为了评价FIX治疗对早期恶变的影响，我们分析了结肠组织中5-羟色胺（5-HT）代谢和识别、异常隐窝病灶（ACF）、增殖过程、微血管、血管内皮生长因子（VEGF）和环氧合酶-2（考克斯-2）表达。雄性Wistar大鼠每天接受FLX管饲法（30 mg/kg）和单剂量的1.2二甲基肼（DMH; i. p.，125 mg/kg）。FIX治疗6周后，我们的结果显示FIX和去甲氟西汀（N-FIX）存在于结肠组织中，这与5-HT水平的显著升高有关（P < 0.05）可能通过阻断SERT mRNA（5-羟色胺再摄取转运体; P < 0.05）导致5-羟吲哚乙酸（5-HIAA）水平降低（P < 0.01）和5-HT 2C受体mRNA表达降低。FIX处理可减少上皮细胞中异型增生ACF的形成（P < 0.01）和增殖过程（P < 0.001）。我们观察到恶性微血管的发展（P < 0.05），VEGF（P < 0.001）和考克斯-2表达（P < 0.01）显著减少。这些结果表明，FIX可能对致癌结肠组织具有抑瘤作用，这可能是由于其对5-HT代谢的调节活性和/或其减少结肠恶性事件的能力。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Fluoxetine (FIX) is a drug commonly used as antidepressant. However, its effects on tumorigenesis remain controversial. Aiming to evaluate the effects of FIX treatment on early malignant changes, we analyzed serotonin (5-HT) metabolism and recognition, aberrant crypt foci (ACF), proliferative process, microvessels, vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) expression in colon tissue. Male Wistar rats received a daily FLX-gavage (30 mg kg(-1)) and, a single dose of 1.2 dimethylhydrazine (DMH; i.p., 125 mg kg(-1)). After 6 weeks of FIX-treatment, our results revealed that FIX and nor-fluoxetine (N-FIX) are present in colon tissue, which was related to significant increase in serotonin (5-HT) levels (P < 0.05) possibly through a blockade in SERT mRNA (serotonin reuptake transporter; P < 0.05) resulting in lower 5-hydroxyindoleacetic acid (5-HIAA) levels (P < 0.01) and, 5-HT2C receptor mRNA expressions. FIX-treatment decreased dysplastic ACF development (P < 0.01) and proliferative process (P < 0.001) in epithelia. We observed a significant decrease in the development of malignant microvessels (P < 0.05), VEGF (P < 0.001), and COX-2 expression (P < 0.01). These findings suggest that FIX may have oncostatic effects on carcinogenic colon tissue, probably due to its modulatory activity on 5-HT metabolism and/or its ability to reduce colonic malignant events. (C) 2011 Elsevier Ireland Ltd. All rights reserved.