Qiu Jianqing, Zhao Ziyi, Suo Hongyan, Paraghamian Sarah E, Hawkins Gabrielle M, Sun Wenchuan, Zhang Xin, Hao Tianran, Deng Beor, Shen Xiaochang, Zhou Chunxiao, Bae-Jump Victoria
Department of Obstetrics and Gynecology, the Second Hospital of Shandong University, Jinan, PR, China.
Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Cancer Biol Ther. 2024 Dec 31;25(1):2325130. doi: 10.1080/15384047.2024.2325130. Epub 2024 Mar 11.
Emerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-tumorigenic or anti-tumorigenic effects on tumor cell growth and invasion in multiple types of cancer. However, the biological role of linoleic acid in endometrial cancer remains unclear. In the present study, we aimed to investigate the functional impact of linoleic acid on cell proliferation, invasion, and tumor growth in endometrial cancer cells and in a transgenic mouse model of endometrial cancer. The results showed that Linoleic acid significantly inhibited the proliferation of endometrial cancer cells in a dose-dependent manner. The treatment of HEC-1A and KLE cells with linoleic acid effectively increased intracellular reactive oxygen species (ROS) production, decreased mitochondrial membrane potential, caused cell cycle G1 arrest, and induced intrinsic and extrinsic apoptosis pathways. The anti-invasive ability of linoleic acid was found to be associated with the epithelial-mesenchymal transition process in both cell lines, including the decreased expression of N-cadherin, snail, and vimentin. Furthermore, treatment of transgenic mice with linoleic acid for four weeks significantly reduced the growth of endometrial tumors and decreased the expression of VEGF, vimentin, Ki67, and cyclin D1 in tumor tissues. Our findings demonstrate that linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cell lines and the mouse model of endometrial cancer, thus providing a pre-clinical basis for future dietary interventions with linoleic acid in endometrial cancer.
新出现的证据为重新编程脂肪酸代谢在子宫内膜癌发生和发展中的整体功能提供了相当多的见解。亚油酸是西方饮食中消耗量最高的必需脂肪酸，已显示出对多种癌症的肿瘤细胞生长和侵袭具有促肿瘤或抗肿瘤作用。然而，亚油酸在子宫内膜癌中的生物学作用仍不清楚。在本研究中，我们旨在研究亚油酸对子宫内膜癌细胞和子宫内膜癌转基因小鼠模型中细胞增殖、侵袭和肿瘤生长的功能影响。结果表明，亚油酸以剂量依赖性方式显著抑制子宫内膜癌细胞的增殖。用亚油酸处理HEC-1A和KLE细胞可有效增加细胞内活性氧（ROS）的产生，降低线粒体膜电位，导致细胞周期G1期阻滞，并诱导内源性和外源性凋亡途径。发现亚油酸的抗侵袭能力与两种细胞系中的上皮-间质转化过程有关，包括N-钙黏蛋白、蜗牛蛋白和波形蛋白表达的降低。此外，用亚油酸处理转基因小鼠四周可显著降低子宫内膜肿瘤的生长，并降低肿瘤组织中VEGF、波形蛋白、Ki67和细胞周期蛋白D1的表达。我们的研究结果表明，亚油酸在子宫内膜癌细胞系和子宫内膜癌小鼠模型中表现出抗增殖和抗侵袭活性，从而为未来用亚油酸进行子宫内膜癌饮食干预提供了临床前依据。
