Eicosopentaneoic Acid and Other Free Fatty Acid Receptor Agonists Inhibit Lysophosphatidic Acid- and Epidermal Growth Factor-Induced Proliferation of Human Breast Cancer Cells.
Eicosopentaneoic Acid and Other Free Fatty Acid Receptor Agonists Inhibit Lysophosphatidic Acid- and Epidermal Growth Factor-Induced Proliferation of Human Breast Cancer Cells.
复制标题
eicosopentaneyac和其他游离脂肪酸受体激动剂抑制溶血磷脂酸和表皮生长因子诱导的人类乳腺癌细胞的增殖。
DOI：
10.3390/jcm5020016
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发表时间：
2016-01-26
影响因子：
3.9
通讯作者：
Meier KE
中科院分区：
文献类型：
--
作者：
Hopkins MM;Zhang Z;Liu Z;Meier KE
ω-3 （n-3）脂肪酸的许多关键作用最近被证明是由游离脂肪酸受体（FFAR）家族中的两个G蛋白偶联受体（gpcr）介导的，FFA1 （GPR40）和FFA4 （GPR120）。n-3脂肪酸在培养和动物实验中抑制人类乳腺癌细胞的增殖。在本研究中，研究了FFA1和FFA4的作用。此外，我们还研究了溶血磷脂酸（LPA）激活的gpcr与表皮生长因子（EGF）激活的酪氨酸激酶受体之间的串扰作用。在MCF-7和MDA-MB-231人乳腺癌细胞系中，LPA和EGF均刺激增殖、Erk活化、Akt活化和CCN1诱导。LPA拮抗剂阻断了LPA和EGF对MCF-7和MDA-MB-231细胞增殖和MCF-7细胞迁移的影响。n-3脂肪酸二十戊酸抑制LPA-和egf诱导的两种细胞系的增殖。两种合成的FFAR激动剂GW9508和TUG-891同样可以抑制LPA-和egf诱导的增殖。这些数据表明，FFA1在两种细胞系中都有表达。结果表明，n-3脂肪酸通过FFARs抑制乳腺癌细胞增殖，并提示FFARs与LPA受体和EGF受体之间存在负交互作用。
Many key actions of ω-3 (n-3) fatty acids have recently been shown to be mediated by two G protein-coupled receptors (GPCRs) in the free fatty acid receptor (FFAR) family, FFA1 (GPR40) and FFA4 (GPR120). n-3 Fatty acids inhibit proliferation of human breast cancer cells in culture and in animals. In the current study, the roles of FFA1 and FFA4 were investigated. In addition, the role of cross-talk between GPCRs activated by lysophosphatidic acid (LPA), and the tyrosine kinase receptor activated by epidermal growth factor (EGF), was examined. In MCF-7 and MDA-MB-231 human breast cancer cell lines, both LPA and EGF stimulated proliferation, Erk activation, Akt activation, and CCN1 induction. LPA antagonists blocked effects of LPA and EGF on proliferation in MCF-7 and MDA-MB-231, and on cell migration in MCF-7. The n-3 fatty acid eicosopentaneoic acid inhibited LPA- and EGF-induced proliferation in both cell lines. Two synthetic FFAR agonists, GW9508 and TUG-891, likewise inhibited LPA- and EGF-induced proliferation. The data suggest a major role for FFA1, which was expressed by both cell lines. The results indicate that n-3 fatty acids inhibit breast cancer cell proliferation via FFARs, and suggest a mechanism involving negative cross-talk between FFARS, LPA receptors, and EGF receptor.