Wu Zhide, Hui Jianping
Department of Geriatrics, the First People's Hospital of Lanzhou City, Lanzhou, China.
Shaanxi University of Chinese Medicine, Xi Xian New Area, Xianyang, China.
J Gastrointest Oncol. 2020 Dec;11(6):1242-1252. doi: 10.21037/jgo-20-406.
Crocin, an active constituent of saffron, has anticancer activity. In this study, we investigated the relationship of Crocin with human gastric epithelial cells induced by 1-methyl-3-nitroso-1-nitroguanidine (MNNG), and explored the underlying mechanism.
, the animal growth and atypical hyperplasia were observed in Sprague-Dawley rats. A cell model was established by treating the human gastric mucosa epithelial cell line GES-1 with MNNG. The effects of Crocin on proliferation, cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT) in GES-1 cells were analyzed using Cell Counting Kit-8, colony formation, flow cytometry, and Transwell assay, respectively. Western blot was used to explore the potential mechanism..
The gastric mucosa of animal model deteriorated obviously, the weight growth rate slowed down, and the atypical hyperplasia of gastric mucosa increased. The GES-1 cells had characteristics of malignant cells such as proliferation, apoptosis, and metastasis ability. It was found that Crocin suppressed the cell proliferation, increased apoptosis, and blocked the cycle arrest in G0/G1 phase simultaneously. Furthermore, Crocin negatively regulated the invasion ability of MNNG-treated GES-1 cells and EMT process. Crocin also increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), decreased TAZ in MNNG-treated GES-1 cells. Interestingly, Crocin regulated the expression of TAZ and yes-associated protein (YAP) by increasing Nrf2 level, as well as their upstream targets, mercaptopyruvate sulfurtransferase (MST) and large tumor suppressor (LATS).
Crocin protected against MNNG-induced malignant transformation through the Nrf2/Hippo signaling pathway, which might be a drug candidate for clinical gastric cancer management.
藏红花素是藏红花的一种活性成分，具有抗癌活性。在本研究中，我们研究了藏红花素与1-甲基-3-亚硝基-1-硝基胍（MNNG）诱导的人胃上皮细胞的关系，并探讨了其潜在机制。
观察Sprague-Dawley大鼠的动物生长和非典型增生情况。用MNNG处理人胃黏膜上皮细胞系GES-1建立细胞模型。分别采用细胞计数试剂盒-8、集落形成、流式细胞术和Transwell实验分析藏红花素对GES-1细胞增殖、细胞周期、凋亡和上皮-间质转化（EMT）的影响。采用蛋白质免疫印迹法探讨潜在机制。
动物模型的胃黏膜明显恶化，体重增长率减慢，胃黏膜非典型增生增加。GES-1细胞具有增殖、凋亡和转移能力等恶性细胞特征。发现藏红花素抑制细胞增殖，增加凋亡，并同时阻断细胞周期停滞于G0/G1期。此外，藏红花素负向调节MNNG处理的GES-1细胞的侵袭能力和EMT过程。藏红花素还增加了核因子红细胞2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）的表达，降低了MNNG处理的GES-1细胞中的TAZ。有趣的是，藏红花素通过增加Nrf2水平调节TAZ和Yes相关蛋白（YAP）的表达，以及它们的上游靶点巯基丙酮酸硫转移酶（MST）和大肿瘤抑制因子（LATS）。
藏红花素通过Nrf2/ Hippo信号通路预防MNNG诱导的恶性转化，这可能是临床胃癌治疗的候选药物。
