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.
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.
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。