Smac的过表达促进肿瘤坏死因子相关凋亡诱导配体（TRAIL）诱导的人肝癌细胞死亡。

Over-expression of Smac promotes TRAIL-induced cell death in human hepatocellular carcinoma.

作者信息

Okano Hiroshi, Shiraki Katsuya, Inoue Hidekazu, Kawakita Tomoyuki, Saitou Yukiko, Enokimura Naoyuki, Yamamoto Norihiko, Sugimoto Kazushi, Fujikawa Katsuhiko, Murata Kazumoto, Nakano Takeshi

机构信息

First Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan.

出版信息

Int J Mol Med. 2003 Jul;12(1):25-8.

PMID:12792804

Abstract

The second mitochondria-derived activator of caspase, Smac, is an apoptosis-related protein. Smac releases inhibition of the IAP family from caspase-3 to induce apoptosis. Smac is expressed in some malignant tumor cells and is released from mitochondria into the cytosol after death receptor stimulation to promote apoptosis of tumor cells. In this study, we found down-regulated Smac protein expression in hepatocellular carcinoma (HCC) tissues, compared to that in non-tumor hepatic tissues. Simultaneously, caspase-3 expression also decreased in HCC tissues. HCC cell lines did not undergo apoptosis after TRAIL stimulation, although Smac was expressed in these HCC cells. Ectopic Smac alone did not induce cell death, but could sensitize HCC cells to TRAIL stimulation. With over-expression of Smac in HCC cells, TRAIL induced by 10% HCC cell death. The role of Smac in apoptosis signaling pathway in HCC cells warrants further study.

摘要

第二种线粒体衍生的半胱天冬酶激活剂Smac是一种与细胞凋亡相关的蛋白质。Smac解除IAP家族对caspase-3的抑制作用以诱导细胞凋亡。Smac在一些恶性肿瘤细胞中表达，在死亡受体刺激后从线粒体释放到细胞质中，以促进肿瘤细胞凋亡。在本研究中，我们发现与非肿瘤肝组织相比，肝细胞癌（HCC）组织中Smac蛋白表达下调。同时，HCC组织中caspase-3表达也降低。尽管Smac在这些HCC细胞中表达，但HCC细胞系在TRAIL刺激后未发生凋亡。单独异位表达Smac不会诱导细胞死亡，但可使HCC细胞对TRAIL刺激敏感。随着Smac在HCC细胞中的过表达，TRAIL诱导10%的HCC细胞死亡。Smac在HCC细胞凋亡信号通路中的作用值得进一步研究。