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表没食子儿茶素-3-没食子酸酯对胆管癌细胞的抗癌活性。

Anticancer activities of epigallocatechin-3-gallate against cholangiocarcinoma cells.

作者信息

Kwak Tae Won, Park Su Bum, Kim Hyun-Jung, Jeong Young-Il, Kang Dae Hwan

机构信息

Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital.

Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Gyeongnam.

出版信息

Onco Targets Ther. 2016 Dec 22;10:137-144. doi: 10.2147/OTT.S112364. eCollection 2017.

Abstract

PURPOSE

Epigallocatechin-3-gallate (EGCG) is an antioxidant agent derived from green tea. Because it has chemopreventive and anti-invasive effect against various cancer cells, EGCG can be used to inhibit proliferation and invasion of cholangiocarcinoma (CCA) cells.

METHODS

The anticancer effects of EGCG were studied using human CCA cells (HuCC-T1). Apoptosis was analyzed by Western blotting. Invasion and migration of cancer cells were assessed with Matrigel and wound healing assays. An animal tumor xenograft model of HuCC-T1 was used to study the in vivo antitumor activities of EGCG.

RESULTS

EGCG effectively inhibited the growth of HuCC-T1 cells with no adverse effects on the viability of 293T cells. EGCG induced apoptotic cell death at 5 µg/mL concentration. It inhibited the expression of mutant p53 and induced apoptotic molecular signals such as Bax/Bcl-2, Caspase, and cytochrome C. Furthermore, EGCG dose-dependently inhibited the activity of matrix metalloproteinase (MMP)-2/9, invasion, and migration. In the animal tumor xenograft model of HuCC-T1 cells, EGCG was subcutaneously administered beside the tumor for local treatment. EGCG efficiently inhibited growth of the tumor and suppressed carcinogenic molecular signals such as Notch1, MMP-2/9, and proliferating cell nuclear antigen.

CONCLUSION

EGCG induced apoptosis of cancer cells without adverse effects on normal cells. EGCG inhibited growth, invasion, and migration of HuCC-T1 cells. We suggest EGCG as a promising candidate for local treatment of CCA.

摘要

目的

表没食子儿茶素-3-没食子酸酯(EGCG)是一种从绿茶中提取的抗氧化剂。由于其对多种癌细胞具有化学预防和抗侵袭作用,EGCG可用于抑制胆管癌细胞(CCA)的增殖和侵袭。

方法

使用人CCA细胞(HuCC-T1)研究EGCG的抗癌作用。通过蛋白质印迹法分析细胞凋亡。用基质胶和伤口愈合试验评估癌细胞的侵袭和迁移。使用HuCC-T1的动物肿瘤异种移植模型研究EGCG的体内抗肿瘤活性。

结果

EGCG有效抑制HuCC-T1细胞的生长,对293T细胞的活力无不良影响。EGCG在5μg/mL浓度时诱导细胞凋亡性死亡。它抑制突变型p53的表达,并诱导凋亡分子信号,如Bax/Bcl-2、半胱天冬酶和细胞色素C。此外,EGCG剂量依赖性地抑制基质金属蛋白酶(MMP)-2/9的活性、侵袭和迁移。在HuCC-T1细胞的动物肿瘤异种移植模型中,将EGCG皮下注射到肿瘤旁进行局部治疗。EGCG有效抑制肿瘤生长,并抑制致癌分子信号,如Notch1、MMP-2/9和增殖细胞核抗原。

结论

EGCG诱导癌细胞凋亡,对正常细胞无不良影响。EGCG抑制HuCC-T1细胞的生长、侵袭和迁移。我们认为EGCG是CCA局部治疗的一个有前景的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f454/5189709/cba6690ec238/ott-10-137Fig1.jpg

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