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下调血管生成素样蛋白 4 抑制结直肠癌的发展。

Knockdown of Angiopoietin-like protein 4 suppresses the development of colorectal cancer.

机构信息

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of gastrointestinal surgery, Sun YAT-SEN Memorial Hospital, Sun YAT-SEN University, NO.107 Yan Jiang Road West, Guangzhou 510120, China.

Department of Agriculture, Jouybar branch, Islamic Azad University, Jouybar, Iran.

出版信息

Cell Mol Biol (Noisy-le-grand). 2020 Jul 31;66(5):117-124.

PMID:33040824
Abstract

Colorectal cancer, is the growth of cancer cells in the part of the colon. Angiopeptin is one of the growth factors in the human body that is particularly effective in the regulatory process. In this research, the regulatory role and its mechanism of Angiopoietin-like protein 4 (ANGPTL4) in colorectal cancer (CRC) metastasis, has been studied. Protein expression of ANGPLT4 was analyzed by immunohistochemistry in tumor samples and adjacent normal specimens of 40 patients with CRC cancer of various phases. A gene knockout test was conducted, two effective siRNA of ANGPTL4, named siRNA1 and siRNA2, were constructed and transfected into two CRC cell lines SW480 and HT-29 to block the expression of ANGPTL4. QRT-PCR and western blotting were used to validate the knockdown efficiency of the mRNA and proteins. Based on the results, the protein expression of ANGPTL4 was increased in human CRC tissues with the development of CRC. Knockdown of ANGPTL4 by siRNA in SW480 and HT-29 cells in vitro inhibited cell proliferation, promoted cell apoptosis, and suppressed the ability of cell migration and invasion. Besides, the sensitivity of CRC cells to Cisplatin was increased in the low ANGPTL4 expression group. ANGPTL4 might be a new potential therapeutic target for patients with CRC.

摘要

结直肠癌是结肠部位的癌细胞生长。血管生成素是人体内一种特别有效的生长因子,在调节过程中发挥作用。在这项研究中,研究了血管生成素样蛋白 4(ANGPTL4)在结直肠癌(CRC)转移中的调节作用及其机制。通过免疫组织化学分析了 40 名 CRC 患者肿瘤样本和相邻正常样本中 ANGPLT4 的蛋白表达。进行了基因敲除试验,构建了两种有效的 ANGPTL4 siRNA,命名为 siRNA1 和 siRNA2,并转染到两个 CRC 细胞系 SW480 和 HT-29 中以阻断 ANGPTL4 的表达。使用 QRT-PCR 和 Western blot 验证了 mRNA 和蛋白的敲低效率。基于这些结果,ANGPTL4 的蛋白表达在 CRC 发展过程中在人 CRC 组织中增加。在体外,siRNA 敲低 SW480 和 HT-29 细胞中的 ANGPTL4 抑制细胞增殖,促进细胞凋亡,并抑制细胞迁移和侵袭能力。此外,在低 ANGPTL4 表达组中,CRC 细胞对顺铂的敏感性增加。ANGPTL4 可能成为 CRC 患者的新的潜在治疗靶点。

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