Ogasawara Sachiko, Akiba Jun, Nakayama Masamichi, Kusano Hironori, Yano Hirohisa
Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Department of Diagnostic Pathology, Kurume University Hospital and Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Biomed Rep. 2016 Dec;5(6):731-736. doi: 10.3892/br.2016.792. Epub 2016 Oct 25.
Soyasapogenol, an aglycon of soyasaponin, ameliorates liver injury induced by concanavalin A in mice. A derivative of soyasapogenol, 22β-methoxyolean-12-ene-3β, 24(4β)-diol (ME3738), was reported to induce the gene expression of interferon (IFN)-β in hepatitis C virus replicon cells. The effect of ME3738 on hepatocellular carcinoma (HCC) cell lines was investigated in the present study. A total of 11 HCC cell lines were cultured in medium containing 0-10 µM ME3738, and after 24, 48, or 72 h of culture, morphological observation and MTT cell growth assays were performed. Furthermore, the effects of ME3738 with or without PEG-IFN-α-2b on cell lines were investigated. Induction of apoptosis was examined on cells treated with 1 µM of ME3738 using an Annexin V assay. The effect of ME3738 (0.63 and 2.5 µM) on cell cycle progression was analyzed on two cell lines. The mice with subcutaneous tumors were divided into four groups: i) Control; ii) ME3738 alone; iii) PEG-IFN-α-2b alone and iv) ME3738+PEG-IFN-α-2b (combination). ME3738 was mixed with food (1.5 mg/g) and was taken orally for 15 days. PEG-IFN-α-2b (1,920 IU/mouse) was subcutaneously injected twice a week for two consecutive weeks. On day 15, the mice were sacrificed and the tumors were resected. A dose-dependent anti-proliferative effect was observed to various degrees in all the HCC cell lines . This inhibitory effect reached its maximal level 24 h after the treatment and the 50% inhibitory dose was between 0.8 and 2.4 µM. The combination treatment did not show a synergistic effect. Induction of apoptosis was not observed. Cell cycle arrest at S-phase was observed in two of the examined cell lines. On day 15, the tumor volume of mice receiving ME3738, PEG-IFN-α-2b, and ME3738+PEG-IFN-α-2b was 69, 30, and 33%, respectively, of the control tumor volume. ME3738 induced antiproliferative effects on the HCC cells and . The data suggested potential clinical application of ME3738.
大豆皂醇是大豆皂苷的苷元，可改善伴刀豆球蛋白A诱导的小鼠肝损伤。据报道，大豆皂醇的一种衍生物22β-甲氧基齐墩果-12-烯-3β，24(4β)-二醇（ME3738）可诱导丙型肝炎病毒复制子细胞中干扰素（IFN）-β的基因表达。本研究调查了ME3738对肝癌（HCC）细胞系的影响。将总共11种HCC细胞系培养于含有0-10µM ME3738的培养基中，培养24、48或72小时后，进行形态学观察和MTT细胞生长测定。此外，还研究了ME3738联合或不联合聚乙二醇干扰素-α-2b对细胞系的影响。使用膜联蛋白V测定法检测用1µM ME3738处理的细胞的凋亡诱导情况。分析了ME3738（0.63和2.5µM）对两种细胞系细胞周期进程的影响。将皮下接种肿瘤的小鼠分为四组：i）对照组；ii）单独使用ME3738组；iii）单独使用聚乙二醇干扰素-α-2b组和iv）ME3738+聚乙二醇干扰素-α-2b（联合）组。将ME3738与食物混合（1.5mg/g），口服15天。聚乙二醇干扰素-α-2b（1920IU/小鼠）每周皮下注射两次，连续注射两周。在第15天，处死小鼠并切除肿瘤。在所有HCC细胞系中均观察到不同程度的剂量依赖性抗增殖作用。这种抑制作用在处理后24小时达到最大水平，50%抑制剂量在0.8至2.4µM之间。联合治疗未显示协同作用。未观察到凋亡诱导现象。在两个检测的细胞系中观察到细胞周期停滞在S期。在第15天，接受ME3738、聚乙二醇干扰素-α-2b和ME3738+聚乙二醇干扰素-α-2b治疗的小鼠的肿瘤体积分别为对照肿瘤体积的69%、30%和33%。ME3738对HCC细胞 和 具有抗增殖作用。数据表明ME3738具有潜在的临床应用价值。
