Department of Gynecology, Fourth Hospital of Hebei Medical University, China.
Department of Gynecology, Fourth Hospital of Hebei Medical University, China.
Arch Biochem Biophys. 2020 May 15;684:108327. doi: 10.1016/j.abb.2020.108327. Epub 2020 Mar 3.
Endometrial carcinoma is a type of gynecological cancer that originates in the endometrial epithelial tissue. Due to its high proliferation and ability to invade muscle tissue, it is one of the most common malignant tumors in the female reproductive system. Fatostatin is a small molecule non-sterol diarylthiazole derivative that acts as a chemical inhibitor of the sterol regulatory-element binding protein (SREBP) pathway. Previous studies have shown that fatostatin has an anti-tumor effect in some cancers. In this study, we investigated the effect of fatostatin on the growth, proliferation, apoptosis, migration and cell cycle of human endometrial carcinoma cells (HEC-1A and AN3 CA cells) using cholecystokinin (CCK) -8 method, clonogenicity assay, wound closure assay, Transwell migration assay and flow cytometer. We also examined its effect on the expression of apoptosis-associated protein (Caspase-3, Caspase-8 and Caspase-9) and level of lipid metabolism-related proteins, free fatty acid, and total cholesterol in cells. The growth of endometrial carcinoma xenografts was measured to confirm the effect of fatostatin in vivo. Our results showed that fatostatin inhibited the growth and proliferation of human endometrial carcinoma cells, changed their cell cycle and induced apoptosis. Based on the preliminary animal experiments, fatostatin also exhibited antitumor activity. The present study adds a new dimension to our understanding of the antitumor effects of fatostatin and provides an experimental basis for its use, and supports its potential value for clinical application.
子宫内膜癌是一种起源于子宫内膜上皮组织的妇科癌症。由于其高增殖能力和侵袭肌肉组织的能力，它是女性生殖系统中最常见的恶性肿瘤之一。法尼醇酯是一种小分子非甾体二芳基噻唑衍生物，作为固醇调节元件结合蛋白（SREBP）途径的化学抑制剂。先前的研究表明，法尼醇酯在一些癌症中具有抗肿瘤作用。在这项研究中，我们使用胆囊收缩素（CCK）-8 法、集落形成实验、划痕闭合实验、Transwell 迁移实验和流式细胞仪研究了法尼醇酯对人子宫内膜癌细胞（HEC-1A 和 AN3CA 细胞）的生长、增殖、凋亡、迁移和细胞周期的影响。我们还检查了它对凋亡相关蛋白（Caspase-3、Caspase-8 和 Caspase-9）表达和细胞内脂质代谢相关蛋白、游离脂肪酸和总胆固醇水平的影响。测量子宫内膜癌异种移植物的生长以确认法尼醇酯在体内的作用。我们的结果表明，法尼醇酯抑制人子宫内膜癌细胞的生长和增殖，改变其细胞周期并诱导细胞凋亡。基于初步的动物实验，法尼醇酯也表现出抗肿瘤活性。本研究为我们对法尼醇酯抗肿瘤作用的认识增添了新的维度，并为其应用提供了实验依据，支持其在临床应用中的潜在价值。
