Cai Zhengxu, Liang Pin, Xuan Jize, Wan Jiajia, Guo Huishu
Department of Internal Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People's Republic of China.
Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People's Republic of China.
Tumour Biol. 2016 Jul;37(7):9111-20. doi: 10.1007/s13277-015-4775-2. Epub 2016 Jan 14.
Esophageal cancer related gene 4 (ECRG4) as a tumor suppressor gene inhibits the growth and development of various tumors. Colorectal cancer (CRC), a common malignant tumor in the digestive tract worldwide, is a leading cause of death. The aim of our study was to assess the tumor-suppressing effect of ECRG4 on CRC and explore its related mechanisms in vitro and in vivo. The expression levels of ECRG4 were measured in colorectal cancer tissues and para-carcinoma tissues. ECRG4 gene was transfected into CRC cells to investigate its effect on cell proliferation by MTT, colony formation assay, and cell cycle analysis. Cell apoptosis was assessed by annexin-V/PI, Hoechst 33342 staining, and analysis of apoptosis-related protein expressions in vitro. The in vivo tumorigenesis assays were performed in nude mice. According to the results, there was a lower expression of ECRG4 in CRC tissues compared with normal tissues, which was strongly associated with histology differentiation and lymph node metastasis. Additionally, overexpression of ECRG4 had a significant inhibitory effect on proliferation and promoted apoptosis in Caco-2 and SW480 cells. Moreover, we found that the overexpression of ECRG4 inhibited tumorigenesis in vivo by diminishing the volume and weight of the tumors and inducing apoptosis of tumor cells. Our study indicates that ECRG4 may be a new potential target and prognostic factor for patients with CRC.
食管癌相关基因4(ECRG4)作为一种肿瘤抑制基因,可抑制多种肿瘤的生长和发展。结直肠癌(CRC)是全球消化道常见的恶性肿瘤,是主要的死亡原因之一。我们研究的目的是评估ECRG4对结直肠癌的肿瘤抑制作用,并在体外和体内探索其相关机制。检测了结直肠癌组织和癌旁组织中ECRG4的表达水平。将ECRG4基因转染到结直肠癌细胞中,通过MTT法、集落形成试验和细胞周期分析来研究其对细胞增殖的影响。通过膜联蛋白V/碘化丙啶、Hoechst 33342染色以及体外凋亡相关蛋白表达分析来评估细胞凋亡。在裸鼠中进行体内肿瘤发生试验。结果显示,与正常组织相比,结直肠癌组织中ECRG4的表达较低,这与组织学分化和淋巴结转移密切相关。此外,ECRG4的过表达对Caco-2和SW480细胞的增殖具有显著抑制作用,并促进细胞凋亡。而且,我们发现ECRG4的过表达通过减小肿瘤体积和重量以及诱导肿瘤细胞凋亡来抑制体内肿瘤发生。我们的研究表明,ECRG4可能是结直肠癌患者新的潜在靶点和预后因素。