Ethyl pyruvate inhibits proliferation and induces apoptosis of hepatocellular carcinoma via regulation of the HMGB1-RAGE and AKT pathways

被引：57

作者：

Cheng, Ping ^{[1
]}

Dai, Weiqi ^{[1
]}

Wang, Fan ^{[1
]}

Lu, Jie ^{[1
]}

Shen, Miao ^{[1
]}

Chen, Kan ^{[1
]}

Li, Jingjing ^{[1
]}

Zhang, Yan ^{[1
]}

Wang, Chengfen ^{[1
]}

Yang, Jing ^{[1
]}

Zhu, Rong ^{[1
]}

Zhang, Huawei ^{[1
]}

Zheng, Yuanyuan ^{[1
]}

Guo, Chuan-Yong ^{[1
]}

Xu, Ling ^{[1
]}

机构：

[1] Tongji Univ Med, Shanghai Peoples Hosp 10, Dept Gastroenterol, Shanghai, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2014年 / 443卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Ethyl pyruvate; Hepatocellular carcinoma; Apoptosis; DEATH BIOMARKERS HMGB1; CANCER-CELLS; MMP-9; GROWTH; OVEREXPRESSION; RECEPTOR; DNASE; RAGE;

D O I：

10.1016/j.bbrc.2013.12.064

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Ethyl pyruvate (EP) was recently identified as a stable lipophilic derivative of pyruvic acid with significant antineoplastic activities. The high mobility group box-B1 (HMGB1)-receptor for advanced glycation end-products (RAGE) and the protein kinase B (Ala) pathways play a crucial role in tumorigenesis and development of many malignant tumors. We tried to observe the effects of ethyl pyruvate on liver cancer growth and explored its effects in hepatocellular carcinoma model. In this study, three hepatocellular carcinoma cell lines were treated with ethyl pyruvate. An MTT colorimetric assay was used to assess the. effects of EP on cell proliferation. Flow cytometry and TUNEL assays were used to analyze apoptosis. Real-time PCR, Western blotting and immunofluorescence demonstrated ethyl pyruvate reduced the HMGB1-RAGE and AKT pathways. The results of hepatoma orthotopic tumor model verified the antitumor effects of ethyl pyruvate in vivo. EP could induce apoptosis and slow the growth of liver cancer. Moreover, EP decreased the expression of HMGB1, RAGE, p-AKT and matrix metallopeptidase-9 (MMP9) and increased the Bax/Bcl-2 ratio. In conclusion, this study demonstrates that ethyl pyruvate induces apoptosis and cell-cycle arrest in G phase in hepatocellular carcinoma cells, plays a critical role in the treatment of cancer. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：1162 / 1168

页数：7

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