Wang Yizi, Ren Fang, Li Bo, Song Zixuan, Chen Peng, Ouyang Ling
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
J Cancer. 2019 Jun 2;10(15):3303-3314. doi: 10.7150/jca.29738. eCollection 2019.
Ellagic acid (EA) is a polyphenol found in several fruits and plants. EA has been reported to exert antitumor activity in many types of cancers. However, the effect and potential molecular mechanism of EA in endometrial cancer are still unclear. Therefore, the aim of this study was to explore the underlying antitumor function and targets by which EA inhibits endometrial cancer. By using multiplatform bioinformatics analysis tools, including DrugBank, STRING, WebGestalt and cBioPortal, the core targets of EA were identified as PIK3CA and PIK3R1. In addition, through transwell assays, EA was strongly found to inhibit cell invasion and migration. Based on CCK8 assays and flow cytometry, EA exhibited a suppressive effect on endometrial cancer cell proliferation by causing cell cycle arrest and inducing apoptosis. The results of real-time PCR confirmed that the expression of PIK3CA and PIK3R was decreased by EA. Furthermore, western blotting analysis demonstrated that EA inhibited PI3K phosphorylation, downregulating the expression of MMP9. , EA suppressed lung metastasis in BALB/c nude mice based on the SUVmax value determined from PET scans and HE staining. According to all these data, it comprehensively demonstrated the inhibitory effect of EA on endometrial cancer through bioinformatics analysis and experimental verification. Our findings suggest that EA may potentially be beneficial for treating endometrial cancer.
鞣花酸（EA）是一种存在于多种水果和植物中的多酚。据报道，EA在多种癌症中具有抗肿瘤活性。然而，EA在子宫内膜癌中的作用及潜在分子机制仍不清楚。因此，本研究的目的是探讨EA抑制子宫内膜癌的潜在抗肿瘤功能及靶点。通过使用包括DrugBank、STRING、WebGestalt和cBioPortal在内的多平台生物信息学分析工具，确定EA的核心靶点为PIK3CA和PIK3R1。此外，通过Transwell实验，强烈发现EA可抑制细胞侵袭和迁移。基于CCK8实验和流式细胞术，EA通过引起细胞周期停滞和诱导凋亡，对子宫内膜癌细胞增殖表现出抑制作用。实时PCR结果证实，EA可降低PIK3CA和PIK3R的表达。此外，蛋白质印迹分析表明，EA抑制PI3K磷酸化，下调MMP9的表达。基于PET扫描和HE染色确定的SUVmax值，EA抑制了BALB/c裸鼠的肺转移。根据所有这些数据，通过生物信息学分析和实验验证全面证明了EA对子宫内膜癌的抑制作用。我们的研究结果表明，EA可能对治疗子宫内膜癌有益。
