Zheng Zhi-Hua, Du Wei, Li Yan-Ju, Gao Mei-Qin, Huang Ai-Min, Liu Jing-Feng
Department of Pathology, Quanzhou Medical College, Quanzhou, Fujian 362100, P.R. China.
Department of Pathology and Institute of Oncology, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China.
Oncol Rep. 2015 Jul;34(1):95-102. doi: 10.3892/or.2015.3976. Epub 2015 May 13.
Apurinic/apyrimidinic endonuclease-1 (APE1) is a protein involved in DNA repair and transcriptional regulation of gene expression. APE1 expression was reported to be correlated with poor prognosis in hepatocellular carcinoma (HCC) patients. Based on our previous study, we hypothesized that APE1 may be involved in the metastatic progression of HCC. Thus, the present study aimed to investigate the knockdown effect of APE1 using shRNA in HCC and demonstrate that silencing of APE1 in MHCC97-H cells can decrease the oncogenic transforming potential in vitro and reduce the growth of HCC tumor xenografts in vivo. Silencing of APE1 expression decreased the cell proliferation and survival, reduced the cell adhesion ability in Matrigel or fibronectin-coated plates and suppressed the cell migration and invasion in a Transwell assay of HCC cells. In the xenograft study, tumor growth was markedly inhibited in the APE1-silenced group. Silencing of APE1 in MHCC97-H cells decreased the oncogenic transforming potential in vitro and reduced the growth of HCC tumor xenografts in vivo. Inhibition of APE1 may present a novel therapeutic approach for the treatment of HCC.
脱嘌呤/脱嘧啶内切核酸酶1（APE1）是一种参与DNA修复和基因表达转录调控的蛋白质。据报道，APE1表达与肝细胞癌（HCC）患者的不良预后相关。基于我们之前的研究，我们推测APE1可能参与了HCC的转移进程。因此，本研究旨在探讨使用短发夹RNA（shRNA）敲低APE1在HCC中的作用，并证明在MHCC97-H细胞中沉默APE1可降低体外致癌转化潜能并减少体内HCC肿瘤异种移植的生长。沉默APE1表达可降低细胞增殖和存活率，降低在基质胶或纤连蛋白包被平板上的细胞黏附能力，并在HCC细胞的Transwell实验中抑制细胞迁移和侵袭。在异种移植研究中，APE1沉默组的肿瘤生长明显受到抑制。在MHCC97-H细胞中沉默APE1可降低体外致癌转化潜能并减少体内HCC肿瘤异种移植的生长。抑制APE1可能为HCC的治疗提供一种新的治疗方法。
