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APE1 在肝癌中的差异表达及其对癌细胞增殖和凋亡的影响。

Differential expression of APE1 in hepatocellular carcinoma and the effects on proliferation and apoptosis of cancer cells.

机构信息

Oncology Surgery Department, Beijing Shijitan Hospital, Capital Medical University (Peking University Ninth School of Clinical Medicine).

出版信息

Biosci Trends. 2018;12(5):456-462. doi: 10.5582/bst.2018.01239.

DOI:10.5582/bst.2018.01239
PMID:30473552
Abstract

This research aimed to investigate the differential expression of apurinic-apyrimidinic endonuclease 1 (APE1) in hepatocellular carcinoma (HCC) tissues and cells and the effects on proliferation and apoptosis of cancer cells. Immunohistochemical techniques were used to detect the expression of APE1 in 80 cases of HCC and the corresponding paracancerous tissue microarrays; meanwhile, Western blots were used to detect the expression of APE1 in both human HCC BEL-7402, BEL-7405, HCC-9204, Hep3B, HepG2, SMMC-7721 and Huh-7 cells, and normal hepatocyte L-02 cells. The relationship between APE1 expression and clinical pathological characteristics of HCC was statistically analyzed. APE1 shRNA vector was constructed in Hep 3B cells to establish a stably transfected cell line, using Western blots to determine the interference efficiency. Cell proliferation activity was detected with MTT assays, while apoptosis was detected with the Annexin V-FITC/PI double-labeling technique. The expression of APE1 in HCC tissues and cells was significantly up-regulated, and its expression was significantly different from TNM staging and histopathological grading. Down-regulation of APE1 expression significantly reduced the proliferative activity and increased the apoptosis rate of Hep 3B cells. In conclusion, APE1 demonstrates cancer progression potential at the clinical, tissue and cell level. It provides a new idea and theoretical basis for APE1-based clinical diagnosis, prognosis determination and molecular targeted therapy in treatment of HCC.

摘要

本研究旨在探讨脱嘌呤脱嘧啶核酸内切酶 1(APE1)在肝细胞癌(HCC)组织和细胞中的差异表达及其对癌细胞增殖和凋亡的影响。采用免疫组织化学技术检测 80 例 HCC 及其相应癌旁组织微阵列中 APE1 的表达;同时,采用 Western blot 检测人 HCC BEL-7402、BEL-7405、HCC-9204、Hep3B、HepG2、SMMC-7721 和 Huh-7 细胞以及正常肝细胞 L-02 中 APE1 的表达。统计分析 APE1 表达与 HCC 临床病理特征的关系。构建 Hep 3B 细胞的 APE1 shRNA 载体,建立稳定转染细胞系,用 Western blot 测定干扰效率。用 MTT 法检测细胞增殖活性,用 Annexin V-FITC/PI 双标记法检测细胞凋亡。HCC 组织和细胞中 APE1 的表达明显上调,其表达与 TNM 分期和组织病理学分级明显不同。下调 APE1 表达显著降低 Hep 3B 细胞的增殖活性,增加其凋亡率。综上所述,APE1 在临床、组织和细胞水平上具有促进癌症进展的潜力。为基于 APE1 的 HCC 临床诊断、预后判断和分子靶向治疗提供了新的思路和理论依据。

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