Tsutsumi Toshihiko, Inoue Manami, Okamoto Yoko, Ishihara Akira, Tokumura Akira
Department of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshinomachi, Nobeoka, Japan.
Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, 1-78-1 Shomachi, Tokushima, Japan.
Dig Dis Sci. 2017 Mar;62(3):669-677. doi: 10.1007/s10620-016-4434-5. Epub 2017 Jan 3.
Oral administration of lysophosphatidic acid (LPA) was shown to attenuate gastric ulceration in rats and mice but aggravate intestinal tumorigenesis in mice.
The present study examined whether dietary LPA induces or prevents development of colorectal tumor in rats.
Kyoto Apc Delta rats fed high-fat diet with or without an LPA-rich soybean phospholipid mixture (LSP, 0.1 or 1%) were treated with azoxymethane and dextran sodium sulfate to induce colorectal tumorigenesis. Rats were killed 15 weeks after azoxymethane treatment, and size, total number, location, and severity of colorectal tumors were assessed. Expression of mRNA of LPA receptors in rat colon tissue was assayed.
Rats fed the diet supplemented with 1% LSP had a higher number of tumors 2-4 mm long compared than those with or without 0.1% LSP. The mean distance of tumors >4 mm long from the anus was significantly higher than those of tumors <2 and 2-4 mm long in rats fed 1% LSP-supplemented diet. Supplementation of the diet with 0.1% LSP decreased mRNA expression of LPA5 in colon tumors of rats.
Dietary supplementation of LPA-rich phospholipids dose-dependently augmented colorectal tumorigenesis. Decreased expression of LPA5 in colon tumors may be relevant to augmented tumorigenesis.
口服溶血磷脂酸（LPA）已被证明可减轻大鼠和小鼠的胃溃疡，但会加重小鼠的肠道肿瘤发生。
本研究检测了饮食中的LPA是否会诱导或预防大鼠结直肠癌的发生。
给携带Apc基因缺失的京都大鼠喂食含或不含富含LPA的大豆磷脂混合物（LSP，0.1%或1%）的高脂饮食，并用氧化偶氮甲烷和葡聚糖硫酸钠处理以诱导结直肠癌发生。在氧化偶氮甲烷处理后15周处死大鼠，评估结直肠癌的大小、总数、位置和严重程度。检测大鼠结肠组织中LPA受体的mRNA表达。
与喂食含0.1% LSP或不含LSP饮食的大鼠相比，喂食添加1% LSP饮食的大鼠有更多2 - 4毫米长的肿瘤。在喂食添加1% LSP饮食的大鼠中，长度>4毫米的肿瘤距肛门的平均距离显著高于长度<2毫米和2 - 4毫米的肿瘤。饮食中添加0.1% LSP可降低大鼠结肠肿瘤中LPA5的mRNA表达。
饮食中补充富含LPA的磷脂会剂量依赖性地增强结直肠癌的发生。结肠肿瘤中LPA5表达降低可能与肿瘤发生增强有关。
