没食子酸表没食子儿茶素酯抑制二甲基肼诱导的大鼠结直肠癌。
Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats.
机构信息
Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210001, Jiangsu Province, China.
Department of Colorectal Surgery, The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, China.
出版信息
World J Gastroenterol. 2020 May 7;26(17):2064-2081. doi: 10.3748/wjg.v26.i17.2064.
BACKGROUND
Epigallocatechin gallate (EGCG) is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention. We explored the inhibitory effect of EGCG on dimethylhydrazine (DMH)-induced colorectal cancer (CRC) using a rat model, predicted the interaction between EGCG and CRC target genes using a database, and explained the EGCG associated target pathways and mechanisms in CRC.
AIM
To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis.
METHODS
DMH (40 mg/kg, s.c., twice weekly for eight weeks) was used to induce CRC in rats. After model establishment, the rats were administered with EGCG (50, 100, or 200 mg/kg, p.o., once daily for eight weeks) and killed 12 and 20 wk after the start of the experiment. Formation of aberrant crypt foci and tumor was studied by histological analysis. Using network pharmacology analysis, candidate and collective targets of EGCG and CRC were identified, and Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG.
RESULTS
At week 12, high-dose EGCG treatment significantly reduced the tumor formation rate, total number of tumors, cancerous and non-cancerous tumors, tumor volume, ascites formation, and aberrant crypt foci count. At week 20, all three doses of EGCG were effective. Seventy-eight collective targets of EGCG and CRC were identified, of which 28 genes were dysregulated in CRC. Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210 (CRC), hsa04115 (p53 signaling pathway), and hsa04151 (PI3K-Akt signaling pathway), GO:0043124 (negative regulation of I-kappaB kinase/NF-kappaB signaling pathway), GO:0043409 (negative regulation of mitogen-activated protein kinase cascade), and GO:2001244 (positive regulation of intrinsic apoptotic signaling pathway) respectively.
CONCLUSION
EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.
背景
表没食子儿茶素没食子酸酯（EGCG）是一种从茶中提取的多羟基酚类化合物，其抗肿瘤作用受到广泛关注。我们使用大鼠模型探索了 EGCG 对二甲基肼（DMH）诱导的结直肠癌（CRC）的抑制作用，使用数据库预测了 EGCG 与 CRC 靶基因的相互作用，并解释了 EGCG 相关的 CRC 靶途径和机制。
目的
通过网络药理学分析了解 EGCG 抑制 CRC 细胞增殖的机制，并鉴定其药理学靶点。
方法
使用 DMH（40mg/kg，皮下注射，每周两次，共 8 周）诱导大鼠 CRC。模型建立后，大鼠给予 EGCG（50、100 或 200mg/kg，口服，每日一次，共 8 周），实验开始后 12 和 20 周处死。通过组织学分析研究了异常隐窝病灶和肿瘤的形成。使用网络药理学分析鉴定 EGCG 和 CRC 的候选和共同靶点，并进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析，以预测 EGCG 改变的途径。
结果
在第 12 周，高剂量 EGCG 治疗显著降低了肿瘤形成率、肿瘤总数、癌性和非癌性肿瘤、肿瘤体积、腹水形成和异常隐窝病灶数。在第 20 周，三种剂量的 EGCG 均有效。鉴定出 78 个 EGCG 和 CRC 的共同靶点，其中 28 个基因在 CRC 中失调。KEGG 和 GO 分析显示，失调基因富集于 hsa05210（CRC）、hsa04115（p53 信号通路）和 hsa04151（PI3K-Akt 信号通路），GO：0043124（I-kappaB 激酶/NF-kappaB 信号通路的负调控），GO：0043409（丝裂原激活蛋白激酶级联的负调控）和 GO：2001244（内在凋亡信号通路的正调控）。
结论
EGCG 通过调节肿瘤发生中涉及的关键途径抑制 DMH 诱导的 CRC 的形成。
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