Department of Biomedical Science, Catholic University of Daegu, Gyeongsan-Si 38430, Republic of Korea.
Department of Biomedical Science, Catholic University of Daegu, Gyeongsan-Si 38430, Republic of Korea.
Phytomedicine. 2018 Mar 15;42:164-171. doi: 10.1016/j.phymed.2018.03.033. Epub 2018 Mar 19.
Pristimerin is a quinonemethide triterpenoid with anti-cancer, anti-angiogenic, anti-inflammatory and anti-protozoal activity. However, the therapeutic role of pristimerin in colitis-associated colorectal carcinogenesis is unknown.
We sought to examine the therapeutic effects of pristimerin on colitis-associated colon cancer induced in mice using azoxymethane (AOM)/dextran sulfate sodium (DSS). The goal was to identify the potential mechanism of action underlying the pharmacological activity of pristimerin.
BALB/c mice were injected with AOM and administered 2% DSS in drinking water. The mice were fed with a diet supplemented with pristimerin (1 to 5 ppm), and colonic tissue was collected at 64 days. The inflammatory status of the colon was assessed by determining the levels of cyclooxygenase-2, inducible nitric oxide synthase and pro-inflammatory cytokines using Western blotting, immunohistochemistry and real-time RT-PCR analyses. Markers of proliferation (proliferating cell nuclear antigen) and apoptosis (TUNEL) were identified in the colon tissues immunohistochemically. The levels of cell cycle-, apoptosis-, and signaling-related proteins were detected by Western blot in colon tissues.
Administration of pristimerin significantly reduced the formation of colonic tumors. Western blot and immunohistological analyses revealed that dietary pristimerin markedly reduced NF-κB-positive cells and levels of inflammation-related proteins in colon tissue. Pristimerin also reduced cell proliferation, induced apoptosis, and decreased the phosphorylation of AKT and FOXO3a in colon tissue.
Pristimerin administration decreased inflammation and proliferation induced by AOM/DSS in colon tissue. It also induced apoptosis and regulated the AKT/FOXO3a signaling pathway. Overall, this study indicates the potential value of pristimerin in suppressing colon tumorigenesis.
普瑞巴林是一种具有抗癌、抗血管生成、抗炎和抗原生动物活性的醌甲醚三萜。然而，普瑞巴林在结肠炎相关结直肠癌发生中的治疗作用尚不清楚。
我们试图使用氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）在小鼠中检查普瑞巴林对结肠炎相关结肠癌的治疗作用。目的是确定普瑞巴林药理活性的潜在作用机制。
BALB/c 小鼠注射 AOM 并用含 2%DSS 的饮用水灌胃。用添加普瑞巴林（1 至 5ppm）的饮食喂养小鼠，并在第 64 天收集结肠组织。通过 Western blot、免疫组化和实时 RT-PCR 分析测定环氧化酶-2、诱导型一氧化氮合酶和促炎细胞因子的水平来评估结肠的炎症状态。通过免疫组织化学鉴定结肠组织中的增殖（增殖细胞核抗原）和凋亡（TUNEL）标志物。通过 Western blot 在结肠组织中检测细胞周期、凋亡和信号相关蛋白的水平。
普瑞巴林给药显著减少了结肠肿瘤的形成。Western blot 和免疫组织化学分析显示，饮食中添加普瑞巴林可显著减少 NF-κB 阳性细胞和结肠组织中炎症相关蛋白的水平。普瑞巴林还减少了细胞增殖，诱导了细胞凋亡，并降低了结肠组织中 AKT 和 FOXO3a 的磷酸化。
普瑞巴林给药可减少 AOM/DSS 诱导的结肠组织炎症和增殖。它还诱导了细胞凋亡并调节了 AKT/FOXO3a 信号通路。总的来说，这项研究表明普瑞巴林在抑制结肠癌发生方面具有潜在价值。
