Permana Sofy, Putri Fityanti Reyudzky, Norahmawati Eviana, Iskandar Agustin, Anggraini Mulyadi Erika Desy, Tri Endharti Agustina
Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia.
Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.
Evid Based Complement Alternat Med. 2020 Jul 19;2020:9418520. doi: 10.1155/2020/9418520. eCollection 2020.
Ulcerative colitis is a major risk factor that increases the occurrence of colorectal cancer. In colorectal cancer due to colitis, intestinal inflammation plays an important role which causes DNA damage. The aim of this study is to investigate the anticancer effect of coelomic fluid of (CFEF) and combinations. Colitis associated colon cancer was induced in BALB/c mice by DSS/AOM. The mice were randomly divided into six groups: group 1 received vehicle (control), groups 2-6 received DSS/AOM, groups 3-5 received cetuximab + CFEF (30, 60, or 120 mg/kgBW), and group 6 received CFEF only. After the 12 week of treatments, the colon tissues were removed for histological examination and immune-fluorescence. Intestinal Epithelial Cells (CECs) were analyzed by flow cytometer. Administration of CFEF significantly decreased the severity of DSS/AOM-induced CAC in a dose-dependent manner. The combinations of CFEF-cetuximab were revealed by histological change. The CFEF significantly reduced the severity scores ( < 0.05). The combinations of CFEF-cetuximab significantly inhibited K-Ras and vimentin expressions, whereas the percentage of RUNX3 significantly increased in CECs. The increasing of RUNX3 could prevent EMT, so that it can decrease K-Ras and vimentin to suppressed cell invasion and migration by CFEF. Our results suggest that CFEF has the therapeutic potential to CAC.
溃疡性结肠炎是增加结直肠癌发生风险的主要因素。在因结肠炎引发的结直肠癌中，肠道炎症起着导致DNA损伤的重要作用。本研究旨在探究海参体腔液（CFEF）及其组合的抗癌效果。通过葡聚糖硫酸钠（DSS）/氧化偶氮甲烷（AOM）诱导BALB/c小鼠患结肠炎相关结肠癌。将小鼠随机分为六组：第1组接受赋形剂（对照），第2 - 6组接受DSS/AOM，第3 - 5组接受西妥昔单抗 + CFEF（30、60或120mg/kg体重），第6组仅接受CFEF。治疗12周后，取出结肠组织进行组织学检查和免疫荧光分析。通过流式细胞仪分析肠道上皮细胞（CECs）。给予CFEF以剂量依赖方式显著降低了DSS/AOM诱导的结肠炎相关结肠癌（CAC）的严重程度。组织学变化显示了CFEF - 西妥昔单抗的组合效果。CFEF显著降低了严重程度评分（P < 0.05）。CFEF - 西妥昔单抗的组合显著抑制了K - Ras和波形蛋白的表达，而CECs中RUNX3的百分比显著增加。RUNX3的增加可预防上皮 - 间质转化（EMT），从而通过CFEF降低K - Ras和波形蛋白以抑制细胞侵袭和迁移。我们的结果表明，CFEF对结肠炎相关结肠癌具有治疗潜力。
