Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Arch Physiol Biochem. 2009 Jul;115(3):127-36. doi: 10.1080/13813450902905899.
The insulin-like growth factor (IGF) system plays a critical role in normal growth and development as well as in malignant states. Most of the biological activities of the IGFs are mediated by the IGF-IR, which is over-expressed in most tumours and cancer cell lines. Fatty acids have critical roles in both systemic physiological processes (e.g. metabolism) and cellular events (e.g. proliferation, apoptosis, signal transduction, and gene expression). Alpha-linolenic acid (ALA) and linoleic acid (LA) are essential fatty acids of the omega-3 and omega-6 families, respectively. The aim of this study was to investigate the potential interactions between fatty acids and the IGF signal transduction pathways, and to evaluate the impact of this interplay on colon cancer cells survival and proliferation. Results of Western blot analyses revealed that ALA and LA enhanced the ligand-induced IGF-IR phosphorylation and, in addition, increased receptor phosphorylation in an IGF-I independent manner. Furthermore, fatty acid treatment led to phosphorylation of downstream signalling molecules, including Akt and Erk. In addition, FACS analysis and apoptosis measurements indicated that ALA and LA have a potential mitogenic effect on HCT116 cells, as reflected by the number of cells in S phase and by a reduction of PARP cleavage, implying a reduction in apoptotic activity. In summary, our results provide evidence that omega-3 and omega-6 fatty acids modulate IGF-I action in colon cancer cells.
胰岛素样生长因子（IGF）系统在正常生长和发育以及恶性状态中起着关键作用。IGFs 的大多数生物学活性都是由 IGF-IR 介导的，IGF-IR 在大多数肿瘤和癌细胞系中过度表达。脂肪酸在全身生理过程（如代谢）和细胞事件（如增殖、凋亡、信号转导和基因表达）中都起着关键作用。α-亚麻酸（ALA）和亚油酸（LA）分别是ω-3 和 ω-6 家族的必需脂肪酸。本研究旨在探讨脂肪酸与 IGF 信号转导途径之间的潜在相互作用，并评估这种相互作用对结肠癌细胞存活和增殖的影响。Western blot 分析结果表明，ALA 和 LA 增强了配体诱导的 IGF-IR 磷酸化，并且以 IGF-I 非依赖性方式增加了受体磷酸化。此外，脂肪酸处理导致下游信号分子如 Akt 和 Erk 的磷酸化。此外，FACS 分析和凋亡测量表明，ALA 和 LA 对 HCT116 细胞具有潜在的促有丝分裂作用，反映在 S 期细胞数量增加和 PARP 切割减少，这意味着凋亡活性降低。总之，我们的结果提供了证据，表明 ω-3 和 ω-6 脂肪酸调节结肠癌细胞中的 IGF-I 作用。
