Institute of Clinical Pathology, Guangodng Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, No. 22 Xinling Road, Shantou 515041, China.
Int J Mol Sci. 2022 May 14;23(10):5509. doi: 10.3390/ijms23105509.
Esophageal squamous cell carcinoma is the most common type of esophageal cancer and accounts for 5% of malignant tumor deaths. Recent research suggests that chronic inflammation and DNA damage may drive the onset of esophageal squamous cell carcinoma, implying that lowering chronic inflammation and DNA damage compounds may provide chemo-prevention. According to epidemiological and experimental evidence, selenium is linked to a lower risk of several malignancies, including esophageal squamous cell carcinoma. However, its exact mechanism is still unclear. In the present study, we used cell lines and a 4-NQO mice model to explore the anti-cancer mechanism of four types of selenium. Our findings indicated that selenium inhibited the proliferation, colony formation, and ROS level of ESCC cell lines in a time-dependent manner. Intriguingly, selenium treatment impeded 4-NQO-induced high-grade intraepithelial neoplasia and reduced the number of positive inflammatory cells by preserving DNA from oxidative damage. In addition, selenium significantly decreased the expression of Ki-67 and induced apoptosis. This study demonstrates that selenium has a significant chemo-preventive effect on ESCC by reducing high-grade dysplasia to low-grade dysplasia. For the first time, selenium was shown to slow down the progression of esophageal cancer by lowering inflammation and oxidative DNA damage.
食管鳞状细胞癌是最常见的食管癌类型，占恶性肿瘤死亡的 5%。最近的研究表明，慢性炎症和 DNA 损伤可能导致食管鳞状细胞癌的发生，这意味着降低慢性炎症和 DNA 损伤化合物可能提供化学预防。根据流行病学和实验证据，硒与几种恶性肿瘤（包括食管鳞状细胞癌）的风险降低有关。然而，其确切机制尚不清楚。在本研究中，我们使用细胞系和 4-NQO 小鼠模型来探索四种硒的抗癌机制。我们的研究结果表明，硒能够以时间依赖性的方式抑制 ESCC 细胞系的增殖、集落形成和 ROS 水平。有趣的是，硒处理通过防止 DNA 氧化损伤来阻止 4-NQO 诱导的高级别上皮内瘤变并减少阳性炎症细胞的数量。此外，硒还显著降低了 Ki-67 的表达并诱导了细胞凋亡。本研究表明，硒通过将高级别发育不良降低为低级别发育不良，对 ESCC 具有显著的化学预防作用。硒首次被证明通过降低炎症和氧化 DNA 损伤来减缓食管癌的进展。
