Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy.
Biotechnology and Microbiology Laboratory, Department of Botany, University of Rajshahi, Rajshahi, Bangladesh.
J Cell Physiol. 2018 Sep;233(9):7143-7156. doi: 10.1002/jcp.26537. Epub 2018 Mar 25.
Uterine leiomyomas (fibroids or myomas) are the most common benign tumors of premenopausal women and new medical treatments are needed. This study aimed to determine the effects of omega-3 fatty acids on the lipid profile, membrane architecture and gene expression patterns of extracellular matrix components (collagen1A1, fibronectin, versican, or activin A), mechanical signaling (integrin β1, FAK, and AKAP13), sterol regulatory molecules (ABCG1, ABCA1, CAV1, and SREBF2), and mitochondrial enzyme (CYP11A1) in myometrial and leiomyoma cells. Myometrial tissues had a higher amount of arachidonic acid than leiomyoma tissues while leiomyoma tissues had a higher level of linoleic acid than myometrial tissues. Treatment of primary myometrial and leiomyoma cells with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) reduced the monounsaturated fatty acid (MUFA) content and increased the polyunsaturated fatty acid (PUFA) content in both cell types. Myometrial and leiomyoma cell membranes were in the liquid-crystalline phase, but EPA- and DHA-treated cells had decreased membrane fluidity. While we found no changes in the mRNA expression of ECM components, EPA and DHA treatment reduced levels of ABCG1, ABCA1, and AKAP13 in both cell types. EPA and DHA also reduced FAK and CYP11A1 expression in myometrial cells. The ability of omega-3 fatty acids to remodel membrane architecture and downregulate the expression of genes involved in mechanical signaling and lipid accumulation in leiomyoma cells offers to further investigate this compound as preventive and/or therapeutic option.
子宫平滑肌瘤(纤维瘤或肌瘤)是绝经前妇女最常见的良性肿瘤,需要新的治疗方法。本研究旨在确定 ω-3 脂肪酸对脂质谱、细胞膜结构以及细胞外基质成分(胶原 1A1、纤维连接蛋白、软骨素聚糖、激活素 A)、机械信号(整合素 β1、FAK、AKAP13)、固醇调节分子(ABCG1、ABCA1、CAV1、SREBF2)和线粒体酶(CYP11A1)的基因表达模式在子宫平滑肌和肌瘤细胞中的作用。与肌瘤组织相比,子宫组织含有更高量的花生四烯酸,而肌瘤组织含有更高水平的亚油酸。用二十碳五烯酸(EPA)或二十二碳六烯酸(DHA)处理原代子宫平滑肌和肌瘤细胞,降低了两种细胞类型中单不饱和脂肪酸(MUFA)的含量,增加了多不饱和脂肪酸(PUFA)的含量。子宫平滑肌和肌瘤细胞膜处于液晶相,但 EPA 和 DHA 处理的细胞降低了细胞膜的流动性。虽然我们没有发现 ECM 成分的 mRNA 表达发生变化,但 EPA 和 DHA 处理降低了两种细胞类型中 ABCG1、ABCA1 和 AKAP13 的水平。EPA 和 DHA 还降低了子宫平滑肌细胞中 FAK 和 CYP11A1 的表达。ω-3 脂肪酸重塑细胞膜结构和下调与机械信号和脂质积累相关的基因表达的能力为进一步研究这种化合物作为预防和/或治疗选择提供了依据。