Lombardi Valter R M, Carrera Iván, Cacabelos Ramón
Department of Health Biotechnology, EuroEspes Biotechnology, 15165 Corunna, Spain.
EuroEspes Biomedical Research Center, Institute for CNS Disorders and Genomic Medicine, 15165 Corunna, Spain.
Exp Ther Med. 2018 Mar;15(3):2547-2556. doi: 10.3892/etm.2017.5681. Epub 2017 Dec 27.
Novel effective chemopreventive agents against cancer are required to improve current therapeutic rates. The aim of the present study was to investigate the anti-carcinogenesis effect of AntiGan, an extract obtained from the European conger eel, , (human tumor cell lines) and (murine model of colitis) models. The potential apoptogenic activity after 24 h of incubation with 10, 25 and 50 µl/ml AntiGan was reported using growth inhibition and apoptosis activity assays. studies were performed in mice by inducing colitis with oral administration of 2% dextran sulphate sodium (DSS) for 5 weeks. Apoptosis was observed in HL-60, Hs 313.T, SW-480, Caco-2 and HT-29 cell lines. The highest level of growth inhibition was observed in Caco-2 (66, 75.8 and 88.1%), HT-29 (56, 73 and 87.6%) and SW-480 (38.5, 61.6, 78.6%) for AntiGan doses of 10, 25 and 50 µl/ml, respectively, compared to untreated cells, while the results of the expression of genes associated with apoptosis indicated a downregulation of B-cell lymphoma 2 (Bcl-2) in all cell lines studied. , morphopathological alterations in the colon were analyzed by immunohistochemical and staining methods. Tumoral markers, including β-catenin, cyclooxygenase 2 and Bcl-2 were expressed in cryptal cells of the dysplastic colonic mucosa, whereas the levels of interferon-γ expression were also increased when no treatment was applied. In the experimental murine model, the optimal concentration of AntiGan for an effective dose-response was 10% in diet. These results suggested that AntiGan displays a powerful anti-inflammatory effect in DSS-induced colitis, acting as a chemopreventive agent against colon carcinogenesis, most likely due to its apoptogenic peptides that contribute to the induction of apoptosis.
需要新型有效的癌症化学预防剂来提高当前的治疗率。本研究的目的是研究从欧洲康吉鳗中提取的提取物AntiGan在人肿瘤细胞系和小鼠结肠炎模型中的抗癌发生作用。使用生长抑制和凋亡活性测定法报告了与10、25和50微升/毫升AntiGan孵育24小时后的潜在凋亡活性。通过口服2%硫酸葡聚糖钠(DSS)诱导小鼠结肠炎5周进行研究。在HL-60、Hs 313.T、SW-480、Caco-2和HT-29细胞系中观察到凋亡。与未处理的细胞相比,对于10、25和50微升/毫升的AntiGan剂量,在Caco-2(分别为66%、75.8%和88.1%)、HT-29(分别为56%、73%和87.6%)和SW-480(分别为38.5%、61.6%、78.6%)中观察到最高水平的生长抑制,而与凋亡相关基因的表达结果表明,在所有研究的细胞系中B细胞淋巴瘤2(Bcl-2)下调。通过免疫组织化学和染色方法分析结肠中的形态病理学改变。肿瘤标志物,包括β-连环蛋白、环氧合酶2和Bcl-2在发育异常的结肠黏膜隐窝细胞中表达,而在未进行治疗时干扰素-γ表达水平也增加。在实验小鼠模型中,饮食中有效剂量反应的AntiGan最佳浓度为10%。这些结果表明,AntiGan在DSS诱导的结肠炎中显示出强大的抗炎作用,作为一种抗结肠癌发生的化学预防剂,最有可能是由于其促凋亡肽有助于诱导凋亡。