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靶向过表达的 CREB 抑制食管鳞状细胞癌细胞生长。

Targeting the overexpressed CREB inhibits esophageal squamous cell carcinoma cell growth.

机构信息

College of Basic Medical Sciences, Zhengzhou University, Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, Henan 450001, P.R. China.

出版信息

Oncol Rep. 2018 Mar;39(3):1369-1377. doi: 10.3892/or.2017.6167. Epub 2017 Dec 19.

Abstract

Although several studies highlight the important role of cAMP-responsive element binding protein (CREB) in tumor progression, little is known concerning the expression and function of CREB in esophageal cancer. In the present study, the expression of CREB was evaluated using a human esophageal squamous cell carcinoma tissue array by immunohistochemical analysis, which was confirmed by western blot analysis of tissues from esophageal cancer, and adjacent esophageal tissue. The role of CREB on esophageal cancer cell growth was analyzed in vitro and in vivo. Results showed that CREB was overexpressed in esophageal squamous cell carcinomas tissues, which was positively correlated with lymph node metastasis and tumor-node-metastasis (TNM) stage of esophageal cancer patients. Downregulating the expression of CREB effectively reduced esophageal cell growth in vitro and in vivo, induced S phase cell cycle arrest, triggered apoptosis and inhibited cell migration and invasion. These findings suggested CREB as an attractive drug target for esophageal cancer.

摘要

虽然有几项研究强调了环磷腺苷反应元件结合蛋白 (CREB) 在肿瘤进展中的重要作用,但关于 CREB 在食管癌中的表达和功能知之甚少。在本研究中,通过免疫组织化学分析评估了 CREB 在人食管鳞状细胞癌组织阵列中的表达,并通过 Western blot 分析对食管癌和相邻食管组织进行了验证。在体外和体内分析了 CREB 对食管癌细胞生长的作用。结果表明,CREB 在食管鳞状细胞癌组织中过度表达,与食管癌患者的淋巴结转移和肿瘤-淋巴结-转移 (TNM) 分期呈正相关。下调 CREB 的表达可有效减少体外和体内食管细胞的生长,诱导 S 期细胞周期停滞,引发细胞凋亡并抑制细胞迁移和侵袭。这些发现表明 CREB 是一种有吸引力的食管癌药物靶点。

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