白藜芦醇对 ApcMin 小鼠苯并(a)芘诱导结肠息肉的化学预防作用。

Chemoprevention of benzo(a)pyrene-induced colon polyps in ApcMin mice by resveratrol.

机构信息

Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA.

出版信息

J Nutr Biochem. 2013 Apr;24(4):713-24. doi: 10.1016/j.jnutbio.2012.04.005. Epub 2012 Aug 11.

Abstract

Human dietary exposure to benzo(a)pyrene (BaP) has generated interest with regard to the association of BaP with gastrointestinal carcinogenesis. Since colon cancer ranks third among cancer-related mortalities, it is necessary to evaluate the effect of phytochemicals on colon cancer initiation and progression. In this study, we investigated the preventive effects of resveratrol (RVT) on BaP-induced colon carcinogenesis in Apc(Min) mouse model. For the first group of mice, 100 μg BaP/kg body weight was administered to mice in peanut oil via oral gavage over a 60-day period. For the second group, RVT was coadministered with BaP at a dose of 45 μg/kg. For the third group, RVT was administered for 1 week prior to BaP exposure for 60 days. Jejunum, colon and liver were collected at 60 days post BaP and RVT exposure; adenomas in jejunum and colon were counted and subjected to histopathology. RVT reduced the number of colon adenomas in BaP+RVT-treated mice significantly compared to that in mice that received BaP alone. While dysplasia of varying degrees was noted in colon of BaP-treated mice, the dysplasias were of limited occurrence in RVT-treated mice. To ascertain whether the tumor inhibition is a result of altered BaP-induced toxicity of tumor cells, growth, apoptosis and proliferation of adenocarcinoma cells were assessed posttreatment with RVT and BaP. Cotreatment with RVT increased apoptosis and decreased cell proliferation to a greater extent than with BaP alone. Overall, our observations reveal that RVT inhibits colon tumorigenesis when given together with BaP and holds promise as a therapeutic agent.

摘要

人体对苯并(a)芘(BaP)的饮食暴露引起了人们的关注,因为 BaP 与胃肠道致癌作用有关。由于结肠癌在癌症相关死亡率中排名第三,因此有必要评估植物化学物质对结肠癌发生和发展的影响。在这项研究中,我们研究了白藜芦醇(RVT)对 Apc(Min)小鼠模型中 BaP 诱导的结肠癌发生的预防作用。对于第一组小鼠,通过口服灌胃将 100μg BaP/kg 体重的 BaP 溶于花生油中,在 60 天内给予小鼠。对于第二组,将 RVT 与 BaP 一起以 45μg/kg 的剂量给药。对于第三组,在 BaP 暴露前 1 周给予 RVT,持续 60 天。在 BaP 和 RVT 暴露 60 天后收集空肠、结肠和肝脏;计数空肠和结肠中的腺瘤并进行组织病理学检查。与单独接受 BaP 的小鼠相比,RVT 处理的 BaP+RVT 处理的小鼠结肠腺瘤数量显著减少。虽然 BaP 处理的小鼠结肠出现不同程度的异型增生,但 RVT 处理的小鼠中异型增生的发生率有限。为了确定肿瘤抑制是否是由于改变了肿瘤细胞的 BaP 诱导毒性所致,在用 RVT 和 BaP 处理后评估了腺癌细胞的生长、凋亡和增殖。与单独使用 BaP 相比,RVT 联合治疗更能促进细胞凋亡和降低细胞增殖。总的来说,我们的观察结果表明,RVT 与 BaP 一起使用可抑制结肠肿瘤发生,并有望成为一种治疗剂。

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