Department of Gastroenterology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
J Cell Physiol. 2019 Aug;234(10):17876-17885. doi: 10.1002/jcp.28418. Epub 2019 Mar 9.
The biological activities of crocin, one of the main bioactive compounds of saffron, include anti-inflammatory, antioxidant, antidepressant, and anticancer effects. Crocin has been shown to trigger the apoptosis of gastric cancer cells, but its effect on the metastasis of gastric cancer cells remains unclear. Krüppel-like factor 5 (KLF5) and hypoxia-inducible factor-1α (HIF-1α) are important transcription factors in the development of gastric cancer. KLF5 and HIF-1α expression were analyzed in gastric cancer tissues and cells. Following exposure to crocin, AGS and HGC-27 gastric cancer cells were assessed with regard to migration, invasion, and epithelial-mesenchymal transition (EMT) as well as the expression of KLF5, HIF-1α, and microRNA-320 (miR-320). The miR-320/KLF5/HIF-1α signaling pathway became the focus for further investigation of the mechanism of crocin in gastric cancer cell migration, invasion, and EMT. KLF5 and HIF-1α expression were elevated in gastric cancer tissues and cells, and KLF5 expression was positively correlated with the HIF-1α level in gastric cancer tissues. Crocin was associated with reduced expression of KLF5 and HIF-1α, whereas miR-320 expression was increased. Crocin also inhibited the migration, invasion, and EMT of gastric cancer cells. Upregulation of KLF5 attenuated crocin's function and elevated HIF-1α expression. Dual-luciferase reporter assay demonstrated that KLF5 was a target gene of miR-320. Crocin modulated KLF5 expression via elevation of miR-320 expression. In conclusion, crocin inhibits the EMT, migration, and invasion of gastric cancer cells, and this activity is mediated through miR-320/KLF5/HIF-1α signaling.
西红花中的主要生物活性化合物之一藏红花素具有抗炎、抗氧化、抗抑郁和抗癌作用。藏红花素已被证明可触发胃癌细胞凋亡，但它对胃癌细胞转移的影响尚不清楚。Krüppel 样因子 5（KLF5）和缺氧诱导因子 1α（HIF-1α）是胃癌发生发展中的重要转录因子。分析了胃癌组织和细胞中的 KLF5 和 HIF-1α 表达。用藏红花素处理 AGS 和 HGC-27 胃癌细胞后，评估其迁移、侵袭和上皮-间充质转化（EMT）以及 KLF5、HIF-1α 和 microRNA-320（miR-320）的表达。miR-320/KLF5/HIF-1α 信号通路成为研究藏红花素在胃癌细胞迁移、侵袭和 EMT 中作用机制的焦点。KLF5 和 HIF-1α 在胃癌组织和细胞中表达上调，且胃癌组织中 KLF5 表达与 HIF-1α 水平呈正相关。藏红花素与 KLF5 和 HIF-1α 表达下调有关，而 miR-320 表达上调。藏红花素还抑制胃癌细胞的迁移、侵袭和 EMT。KLF5 上调减弱了藏红花素的功能，并升高了 HIF-1α 表达。双荧光素酶报告基因实验表明，KLF5 是 miR-320 的靶基因。藏红花素通过上调 miR-320 表达来调节 KLF5 表达。总之，藏红花素抑制胃癌细胞的 EMT、迁移和侵袭，这种活性是通过 miR-320/KLF5/HIF-1α 信号通路介导的。
