Reprogramming of fatty acid metabolism promotes cell growth and metastasis through a variety of processes that stimulate signaling molecules, energy storage, and membrane biosynthesis in endometrial cancer. Oleic acid is one of the most important monounsaturated fatty acids in the human body, which appears to have both pro- and anti-tumorigenic activities in various pre-clinical models. In this study, we evaluated the potential anti-tumor effects of oleic acid in endometrial cancer cells and theLKB1fl/flp53fl/flmouse model of endometrial cancer. Oleic acid increased lipogenesis, inhibited cell proliferation, caused cell cycle G1 arrest, induced cellular stress and apoptosis, and suppressed invasion in endometrial cancer cells. Targeting of diacylglycerol acyltransferases 1 and 2 effectively increased the cytotoxicity of oleic acid. Moreover, oleic acid significantly increased the expression of wild-type PTEN, and knockdown of PTEN by shRNA partially reversed the anti-proliferative and anti-invasive effects of oleic acid. Inhibition of the AKT/mTOR pathway by ipatasertib effectively increased the anti-tumor activity of oleic acid in endometrial cancer cells. Oleic acid treatment (10 mg/kg, daily, oral) for four weeks significantly inhibited tumor growth by 52.1% in theLKB1fl/flp53fl/flmice. Our findings demonstrated that oleic acid exhibited anti-tumorigenic activities, dependent on the PTEN/AKT/mTOR signaling pathway, in endometrial cancer.
脂肪酸代谢重编程通过刺激子宫内膜癌中信号分子、能量储存和膜生物合成的多种过程促进细胞生长和转移。油酸是人体中最重要的单不饱和脂肪酸之一，在多种临床前模型中显示出兼具促肿瘤和抗肿瘤活性。本研究评估了油酸在子宫内膜癌细胞及LKB1fl/flp53fl/fl子宫内膜癌小鼠模型中的潜在抗肿瘤效应。油酸能增加脂肪生成、抑制细胞增殖、引起细胞周期G1期阻滞、诱导细胞应激与凋亡，并抑制子宫内膜癌细胞的侵袭能力。靶向二酰基甘油酰基转移酶1和2能有效增强油酸的细胞毒性。此外，油酸显著增加野生型PTEN的表达，而通过shRNA敲低PTEN可部分逆转油酸的抗增殖和抗侵袭作用。伊帕塞替对AKT/mTOR通路的抑制有效增强了油酸在子宫内膜癌细胞中的抗肿瘤活性。在LKB1fl/flp53fl/fl小鼠模型中，每日口服10 mg/kg油酸治疗四周可使肿瘤生长显著抑制52.1%。我们的研究结果表明，油酸在子宫内膜癌中通过PTEN/AKT/mTOR信号通路依赖性机制发挥抗肿瘤活性。
肿瘤(癌症)患者之家