Department of General Surgery, the First Hospital of Jilin University, Changchun, Jilin 130021, PR China.
Oncol Rep. 2013 Jun;29(6):2303-10. doi: 10.3892/or.2013.2398. Epub 2013 Apr 9.
Signal transducer and activator of transcription 1 (STAT1) regulates cell proliferation and survival. The present study aimed to investigate the role of STAT1 in the development and progression of human hepatocellular carcinoma (HCC). The levels of STAT1 expression in 36 HCC and 12 non-HCC liver tissues were examined by immunohistochemistry. The effect of STAT1 overexpression or silencing on the proliferation and apoptosis of HCC cells was determined by MTT and flow cytometric assays. The effect of STAT1 overexpression or silencing on the levels of p53 and cyclin E expression was determined by quantitative PCR and western blot assays. The level of STAT1 expression in the HCC tissues was significantly lower compared to the level in the non-HCC liver tissues and was negatively associated with the histological grade of HCC and serum HBsAg, anti-HCV and α-fetoprotein positivity in HCC patients. Induction of STAT1 overexpression significantly inhibited HepG2 cell proliferation and enhanced HCC cell apoptosis, accompanied by upregulation of p53 expression and STAT1 phosphorylation, but a reduction in cyclin E expression in HepG2 cells. In contrast, knockdown of STAT1 by introduction of STAT1-specific siRNA promoted HepG2 cell proliferation, but inhibited HCC cell apoptosis, accompanied by significant downregulation of p53 expression, but enhancement of cyclin E expression in vitro. Our data suggest that STAT1 may inhibit HCC growth by regulating p53-related cell cycling and apoptosis.
信号转导子和转录激活子 1（STAT1）调节细胞增殖和存活。本研究旨在探讨 STAT1 在人类肝细胞癌（HCC）发生和发展中的作用。通过免疫组织化学法检测 36 例 HCC 和 12 例非 HCC 肝组织中 STAT1 的表达水平。通过 MTT 和流式细胞术检测 STAT1 过表达或沉默对 HCC 细胞增殖和凋亡的影响。通过定量 PCR 和 Western blot 检测 STAT1 过表达或沉默对 p53 和细胞周期蛋白 E 表达水平的影响。与非 HCC 肝组织相比，HCC 组织中 STAT1 的表达水平明显降低，且与 HCC 患者的组织学分级以及血清 HBsAg、抗 HCV 和 α-胎蛋白阳性呈负相关。诱导 STAT1 过表达显著抑制 HepG2 细胞增殖并增强 HCC 细胞凋亡，同时伴有 p53 表达和 STAT1 磷酸化上调，但细胞周期蛋白 E 表达下调。相反，通过引入 STAT1 特异性 siRNA 敲低 STAT1 促进 HepG2 细胞增殖，但抑制 HCC 细胞凋亡，同时伴有 p53 表达显著下调，但细胞周期蛋白 E 表达上调。我们的数据表明，STAT1 可能通过调节 p53 相关的细胞周期和凋亡来抑制 HCC 的生长。
