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低毒外源性芳烃受体调节剂3,3'-二吲哚甲烷对小鼠胃癌的抑制作用

Inhibitory effect of the low-toxic exogenous aryl hydrocarbon receptor modulator 3'3-diindolylmethane on gastric cancer in mice.

作者信息

Su Mingli, Qian Chenchen, Hu Yumin, Lu Wenhua, Huang Rongkang, Chen Minhu, Chen Jie

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.

Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.

出版信息

Oncol Lett. 2017 Dec;14(6):8100-8105. doi: 10.3892/ol.2017.7185. Epub 2017 Oct 16.

Abstract

3'3-Diindolylmethane (DIM) has been proved to exhibit anticancer properties in many solid tumors. In our previous study, we demonstrated that DIM inhibited SGC7901 cell proliferation by inducing apoptosis and delaying cell cycle progression. Herein, we further explored the anti-tumor effect of DIM on SGC-7901 tumor bearing mice. Tumors were excised, weighed, and tested by western blot and TdT-UTP nick-end labeling (TUNEL) assay. Blood samples were collected for biochemical analysis. The expression levels of AhR and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) protein were evaluated by western-blot assay. Our data show that with the increase of DIM dose (0, 5, 10, 20 mg/kg/day), AhR protein gradually decreased as CYP1A1 protein increased. The weight of the tumors found in the treated animals was significantly lower than that of the control group (0.845±0.096 vs. 1.275±0.236 g, 0.768±0.161 vs. 1.275±0.236 g, 0.607±0.106 vs. 1.275±0.236 g, P<0.05). TUNEL test showed that DIM induced increased apoptosis in the treatment groups in a dose-dependent manner. Blood tests also indicated that DIM showed no toxic effect on animal weight or liver and kidney function. These results indicated that DIM agent could be a safe and potent drug in therapy of gastric cancer.

摘要

3,3'-二吲哚甲烷(DIM)已被证明在许多实体瘤中具有抗癌特性。在我们之前的研究中,我们证明DIM通过诱导凋亡和延迟细胞周期进程来抑制SGC7901细胞增殖。在此,我们进一步探讨了DIM对荷SGC-7901肿瘤小鼠的抗肿瘤作用。切除肿瘤,称重,并通过蛋白质免疫印迹法和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)试验进行检测。采集血样进行生化分析。通过蛋白质免疫印迹法评估芳烃受体(AhR)和细胞色素P450 1A1(CYP1A1)蛋白的表达水平。我们的数据表明,随着DIM剂量(0、5、10、20 mg/kg/天)的增加,AhR蛋白逐渐减少,而CYP1A1蛋白增加。在接受治疗的动物中发现的肿瘤重量明显低于对照组(0.845±0.096 vs. 1.275±0.236 g,0.768±0.161 vs. 1.275±0.236 g,0.607±0.106 vs. 1.275±0.236 g,P<0.05)。TUNEL试验表明,DIM以剂量依赖性方式诱导治疗组凋亡增加。血液检测还表明,DIM对动物体重或肝肾功能没有毒性作用。这些结果表明,DIM制剂可能是一种治疗胃癌的安全有效的药物。

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