Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhang Zhi-dong Road, Wuhan, 430060, Hubei Province, People's Republic of China.
Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, People's Republic of China.
Dig Dis Sci. 2018 Jan;63(1):126-134. doi: 10.1007/s10620-017-4856-8. Epub 2017 Dec 2.
Thymoquinone (TQ) is the major constituent of Nigella sativa seed and has shown biological activity in various human carcinomas. However, few studies have reported its effect on esophageal carcinoma (EC).
To explore the chemosensitive effect and mechanism of TQ in augmentation of cisplatin (DDP)-induced apoptosis of EC, both in vitro and in vivo.
The viability and apoptosis of esophageal carcinoma cells were detected by the Cell Counting Kit-8 assay, flow cytometry, and Hoechst 33258 staining. The expression levels of JAK2, p-JAK2, STAT3, p-STAT3, Bax, Bcl-2, Cyclin D1, Survivin, and caspase-3, 7, 9 were evaluated by western blot analysis. The histological changes were examined by TUNEL technique and immunohistochemical analysis.
TQ enhanced the proapoptotic effect of DDP in human esophageal carcinoma cell line Eca-109, while blocking the activation of JAK2/STAT3 signaling pathway. The apoptosis of esophageal carcinoma cells was induced via blocking the activation of JAK2/STAT3 by using a molecular inhibitor (WP1066). Consistent with the in vivo and in vitro results, TQ increased cellular apoptosis and enriched the chemosensitivity of DDP.
TQ along with DDP may regulate the progression of EC and has potential to be a chemotherapeutic agent in EC.
百里醌（TQ）是黑种草种子的主要成分，已在各种人类癌中显示出生物活性。然而，很少有研究报道其对食管癌（EC）的作用。
在体内和体外探索 TQ 对顺铂（DDP）诱导的食管癌细胞凋亡的增敏作用及其机制。
通过细胞计数试剂盒-8 测定法、流式细胞术和 Hoechst 33258 染色检测食管癌细胞的活力和凋亡。通过 Western blot 分析评估 JAK2、p-JAK2、STAT3、p-STAT3、Bax、Bcl-2、Cyclin D1、Survivin 和 caspase-3、7、9 的表达水平。通过 TUNEL 技术和免疫组织化学分析检查组织学变化。
TQ 增强了人食管癌细胞系 Eca-109 中 DDP 的促凋亡作用，同时阻断了 JAK2/STAT3 信号通路的激活。通过使用分子抑制剂（WP1066）阻断 JAK2/STAT3 的激活，诱导食管癌细胞凋亡。与体内和体外结果一致，TQ 增加了细胞凋亡并增加了 DDP 的化疗敏感性。
TQ 与 DDP 一起可能调节 EC 的进展，并有可能成为 EC 的化疗药物。
