姜黄素通过AKT-PTEN-FOXO4信号通路诱导p53基因缺失的肝癌细胞系Hep3B凋亡。
Curcumin Induces p53-Null Hepatoma Cell Line Hep3B Apoptosis through the AKT-PTEN-FOXO4 Pathway.
作者信息
Liou An-Ting, Chen Mei-Fang, Yang Chu-Wen
机构信息
Department of Microbiology, Soochow University, Shihlin, Taipei 111, Taiwan.
Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan.
出版信息
Evid Based Complement Alternat Med. 2017;2017:4063865. doi: 10.1155/2017/4063865. Epub 2017 Jul 9.
OBJECTIVE
Curcumin (diferuloylmethane) is a yellow-colored polyphenol with antiproliferative and proapoptotic activities to various types of cancer cells. This study explored the mechanism by which curcumin induces p53-null hepatoma cell apoptosis.
RESULTS
AKT, FOXO1, and FOXO3 proteins were downregulated after curcumin treatment. Conversely, PTEN was upregulated. Subcellular fractionations revealed that the FOXO4 protein translocated from cytosol into the nucleus after curcumin treatment. Overexpression of FOXO4 increases the sensitivity of Hep3B cells to curcumin. Knockdown of the FOXO4 gene by siRNA inhibits the proapoptotic effects of curcumin on Hep3B cell.
CONCLUSIONS
This study revealed the AKT/PTEN/FOXO4 pathway as a potential candidate of target for treatment of p53-null liver cancers.
目的
姜黄素（二阿魏酰甲烷）是一种黄色多酚，对多种癌细胞具有抗增殖和促凋亡活性。本研究探讨了姜黄素诱导p53基因缺失的肝癌细胞凋亡的机制。
结果
姜黄素处理后，AKT、FOXO1和FOXO3蛋白表达下调。相反，PTEN表达上调。亚细胞分级分离显示，姜黄素处理后FOXO4蛋白从细胞质转移到细胞核。FOXO4过表达增加了Hep3B细胞对姜黄素的敏感性。用小干扰RNA敲低FOXO4基因可抑制姜黄素对Hep3B细胞的促凋亡作用。
结论
本研究揭示了AKT/PTEN/FOXO4通路是治疗p53基因缺失肝癌的潜在靶点。
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