Preventive effect of oral hangeshashinto (TJ-14) on the development of reflux-induced esophageal cancer
Preventive effect of oral hangeshashinto (TJ-14) on the development of reflux-induced esophageal cancer
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DOI：
10.1016/j.surg.2018.02.003
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发表时间：
2018-07-01
期刊：
影响因子：
3.8
通讯作者：
Ohta, Tetsuo
中科院分区：
文献类型：
--
作者：
Miyashita, Tomoharu;Kono, Toru;Ohta, Tetsuo
背景资料：前列腺素E2是促进肿瘤发展的潜在产物之一，也是M2表型巨噬细胞的强诱导剂，其在免疫抑制的微环境中促进肿瘤发展。据报道，日本传统药物（汉方药）Hangeshashinto（TJ-14）通过减少前列腺素E2，可有效预防化疗引起的口腔粘膜炎。我们先前开发了一种手术大鼠食管癌反流模型，并使用这种成熟的动物模型来研究TJ-14在预防食管癌中的作用。我们还评估了TJ-14对前列腺素E2生产的下调的影响，利用食管鳞状细胞癌细胞系暴露于bileacid.Methods：一个端侧食管空肠吻合术进行反流模型。随后给予每日口服饮食，包括饮食掺入TJ-14或作为对照组的标准饮食。术后40周处死大鼠。组织学评估食管癌、Barrett化生和增生性增生的发生率。CD 163是一种M2表型巨噬细胞标志物，用免疫组织化学法进行评估。前列腺素E2酶免疫分析和乳酸脱氢酶测定进行鹅去氧胆酸或胃食管反流内容物暴露于食管鳞状细胞癌细胞line.Results：67%的对照组（n=12）发展为食管癌，但动物接受TJ-14（n=10）的癌症发病率为10%（P= 0.007）。在对照组中83%的大鼠和TJ-14组中50%的大鼠中发现巴雷特化生，表明TJ-14具有保护性趋势（P=.095）。所有大鼠均出现增生性增生。与对照组相比，TJ-14组中Barrett化生和食管癌病变中M2表型巨噬细胞的数量显著减少。结论：TJ-14可降低反流诱导的食管癌发生率和M2巨噬细胞浸润，抑制食管癌细胞PGE 2的产生。关于TJ-14作为食管癌化学预防剂的潜在临床用途，需要进一步研究。(C)2018作者（S）爱思唯尔公司出版这是CC BY-NC-ND许可下的开放获取文章。(http：//creativecommons.org/licenses/by-nc-nd/4.0/）
Background: Prostaglandin E2 is one of the potential products that promotes development of tumors and also is a strong inducer of M2 phenotype macrophages, which contribute to tumor development in the immunosuppressed microenvironment. Hangeshashinto (TJ-14), a Japanese traditional medicine (Kampo medicine), has been reported to be effective in preventing chemotherapy-induced oral mucositis through the reduction of prostaglandin E2. We previously developed a surgical rat reflux model of esophageal cancer and used this well-established animal model to investigate the action of TJ-14 in preventing esophageal cancer. We also assessed the effect of TJ-14 on the downregulation of prostaglandin E2 production, utilizing esophageal squamous cell carcinoma cell line exposed to bile acid.Methods: An end-to-side e sophagojejunostomy was performed for the reflux model. A daily oral diet was subsequently administered, consisting of either diet-incorporated TJ-14 or standard diet as a control group. The rats were killed at 40 weeks after surgery. The incidence of esophageal cancer, Barrett's metaplasia, and proliferative hyperplasia were assessed histologically. CD163, a M2 phenotype macrophage marker, was assessed with immunohistochemistry. Prostaglandin E2 enzyme immunoassay and lactate dehydrogenase assay were performed on chenodeoxycholic acid or gastroesophageal reflux contents exposed to esophageal squamous cell carcinoma cell line.Results: Sixty-seven percent of the controls (n=12) developed esophageal cancer, but animals that received TJ-14 (n=10) had a cancer incidence of 10% (P=.007). Barrett's metaplasia was found in 83% of the rats in the control group and 50% of the rats in the TJ-14 indicating a protective tendency of TJ-14 (P=.095). All of the rats developed proliferative hyperplasia. The number of M2 phenotype macrophage were significantly decreased in the TJ-14 group compared to the control group in both Barrett's metaplasia and esophageal cancer lesions. TJ-14 inhibited chenodeoxycholic acid or gastroesophageal reflux content induced prostaglandin E2 production in esophageal squamous cell carcinoma cell.Conclusion: TJ-14 reduced the incidence of reflux-induced esophageal cancer and the infiltration of M2 macrophages in a surgical rat model or suppressed prostaglandin E2 production in esophageal squamous cell carcinoma cell. Further investigation is required regarding the potential clinical use of TJ-14 as an esophageal cancer chemopreventive agent. (C) 2018 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)