Zhang Yifang, Zhang Lili, Sun Hengzi, Lv Qingtao, Qiu Chunping, Che Xiaoxia, Liu Zhiming, Jiang Jie
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China; Department of Obstetrics and Gynecology, Affiliated Hospital of Taishan Medical University, Tai'an, Shandong 271000, P.R. China.
Department of Ultrasonography, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250012, P.R. China.
Oncol Lett. 2017 Feb;13(2):731-737. doi: 10.3892/ol.2016.5480. Epub 2016 Dec 12.
The morbidity and mortality associated with endometrial cancer (EC) has increased in recent years. Regarded as a tumor suppressor, forkhead transcription factor 1 (FOXO1) has various biological activities and participates in cell cycle progression, apoptosis and differentiation. Notably, FOXO1 also functions in the regulation of lipogenesis and energy metabolism. Lipogenesis is a feature of cancer and is upregulated in EC. Sterol regulatory element-binding protein 1 (SREBP1) is a transcription factor that is also able to regulate lipogenesis. Increased expression of SREBP1 is directly correlated with malignant transformation of tumors. A previous study demonstrated that SREBP1 was highly expressed in EC and directly resulted in tumorigenesis. However, the association between FOXO1 and SREBP1 in EC is not clear. In the present study, lentiviruses overexpressing FOXO1 were used in cell transfection and transduction. Cell viability assays demonstrated that the overexpression of FOXO1 was able to suppress cell proliferation significantly in Ishikawa and AN3 CA cell lines. In addition, FOXO1 overexpression significantly inhibited cell migration and invasion ability . In xenograft models, overexpression of FOXO1 suppressed cell tumorigenesis, and western blot analysis demonstrated that SREBP1 expression was markedly reduced in the FOXO1-overexpressing cells. It may therefore be concluded that FOXO1 is able to inhibit the proliferative capacity of cells and , in addition to the migratory and invasive capacities by directly targeting SREBP1.
近年来，子宫内膜癌（EC）的发病率和死亡率有所上升。叉头转录因子1（FOXO1）被视为一种肿瘤抑制因子，具有多种生物学活性，参与细胞周期进程、凋亡和分化。值得注意的是，FOXO1还在脂肪生成和能量代谢的调节中发挥作用。脂肪生成是癌症的一个特征，在子宫内膜癌中上调。固醇调节元件结合蛋白1（SREBP1）是一种转录因子，也能够调节脂肪生成。SREBP1表达增加与肿瘤的恶性转化直接相关。先前的一项研究表明，SREBP1在子宫内膜癌中高表达，并直接导致肿瘤发生。然而，FOXO1与子宫内膜癌中SREBP1之间的关联尚不清楚。在本研究中，使用过表达FOXO1的慢病毒进行细胞转染和转导。细胞活力测定表明，FOXO1的过表达能够显著抑制Ishikawa和AN3 CA细胞系中的细胞增殖。此外，FOXO1过表达显著抑制细胞迁移和侵袭能力。在异种移植模型中，FOXO1过表达抑制细胞肿瘤发生，蛋白质印迹分析表明，在过表达FOXO1的细胞中SREBP1表达明显降低。因此可以得出结论，FOXO1能够通过直接靶向SREBP1来抑制细胞的增殖能力以及迁移和侵袭能力。
