Sato Hidenobu, Wu Yunyan, Kato Yukio, Liu Qiang, Hirai Hideaki, Yoshizawa Tadashi, Morohashi Satoko, Watanabe Jun, Kijima Hiroshi
Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan.
Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734‑8553, Japan.
Mol Med Rep. 2017 Jul;16(1):43-48. doi: 10.3892/mmr.2017.6571. Epub 2017 May 11.
Differentiated embryonic chondrocyte expressed gene 1 (DEC1) and differentiated embryonic chondrocyte expressed gene 2 (DEC2) belong to the Hairy/Enhancer of Split subfamily of basic helix‑loop‑helix factors. Previous studies have demonstrated that DEC proteins are involved in the regulation of circadian rhythms, response to hypoxia, and tumorigenesis. However, the roles of DEC1 and DEC2 in apoptosis of esophageal carcinoma remain unclear. In the present study, alterations in expression of apoptosis‑related markers in human esophageal squamous cell carcinoma TE‑11 cells treated with cisplatin were examined by western blot, while overall cell viability and apoptosis were analyzed by MTS assay and hematoxylin and eosin staining, respectively. Following cisplatin treatment, expression of DEC2 was downregulated, whereas expression of DEC1 was upregulated. DEC2 overexpression during cisplatin treatment markedly inhibited expression of the pro‑apoptotic factor Bim and slightly increased the anti‑apoptotic factor Bcl‑xL. However, overexpression of DEC1 during cisplatin treatment failed to affect expression of these markers. Additionally, overexpression of DEC2 improved cell viability and decreased cell apoptosis induced by cisplatin. These results suggested that DEC2 exhibits anti‑apoptotic effects in TE‑11 esophageal squamous cell carcinoma cells. Inhibiting DEC2 may therefore have therapeutic potential for the treatment of esophageal cancer, in combination with cisplatin.
分化型胚胎软骨细胞表达基因1（DEC1）和分化型胚胎软骨细胞表达基因2（DEC2）属于碱性螺旋-环-螺旋转录因子的Hairy/Enhancer of Split亚家族。先前的研究表明，DEC蛋白参与昼夜节律调节、缺氧反应和肿瘤发生。然而，DEC1和DEC2在食管癌凋亡中的作用仍不清楚。在本研究中，通过蛋白质印迹法检测顺铂处理的人食管鳞状细胞癌TE-11细胞中凋亡相关标志物的表达变化，同时分别通过MTS法和苏木精-伊红染色分析细胞的总体活力和凋亡情况。顺铂处理后，DEC2的表达下调，而DEC1的表达上调。顺铂处理期间DEC2的过表达显著抑制促凋亡因子Bim的表达，并略微增加抗凋亡因子Bcl-xL的表达。然而，顺铂处理期间DEC1的过表达未能影响这些标志物的表达。此外，DEC2的过表达提高了细胞活力，并减少了顺铂诱导的细胞凋亡。这些结果表明，DEC2在TE-11食管鳞状细胞癌细胞中具有抗凋亡作用。因此，抑制DEC2可能与顺铂联合使用对食管癌具有治疗潜力。
