Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea.
Nutrients. 2018 Nov 2;10(11):1621. doi: 10.3390/nu10111621.
The ω3-polyunsaturated fatty acid docosahexenoic acid (DHA) is known to induce apoptosis of cancer cells. In this study, DHA was shown to reduce viability of pancreatic cancer cells (PANC-1) by inducing DNA fragmentation, activating caspase-3, and increasing the ratio of Bax/Bcl-2. To determine the DHA mechanism of action, the impact of DHA on the activation of the key signaling proteins epidermal growth factor receptor (EGFR), signal transducer and activator of transcription factor 3 (STAT3), nuclear transcription factor-κB (NF-κB), and IκBα in PANC-1 cells was probed. The observed DHA suppression of NF-κB DNA-binding activity was found to result from reduced IκBα phosphorylation. The observed DHA-induced suppression of STAT3 activation was found to be the result of suppressed EGFR activation, which derives from the inhibitory effect of DHA on the integrity of localization of EGFR to cell membrane lipid rafts. Since the activation of STAT3 and NF-κB mediates the expression of survival genes cyclin D1 and survivin, DHA induced apoptosis by suppressing the STAT3/NF-κB-cyclin D1/survivin axis. These results support the proposal that DHA-induced apoptosis of pancreatic cells occurs via disruption of key pro-cell survival signaling pathways. We suggest that the consumption of DHA-enriched foods could decrease the incidence of pancreatic cancer.
ω3 多不饱和脂肪酸二十二碳六烯酸（DHA）已知可诱导癌细胞凋亡。在这项研究中，DHA 通过诱导 DNA 片段化、激活半胱天冬酶-3 和增加 Bax/Bcl-2 比值来降低胰腺癌细胞（PANC-1）的活力。为了确定 DHA 的作用机制，研究了 DHA 对胰腺癌细胞中关键信号蛋白表皮生长因子受体 (EGFR)、信号转导和转录激活因子 3 (STAT3)、核转录因子-κB (NF-κB) 和 IκBα 的激活的影响。观察到 DHA 对 NF-κB DNA 结合活性的抑制作用是由于 IκBα 磷酸化减少所致。观察到 DHA 诱导的 STAT3 激活抑制是由于 EGFR 激活受抑制所致，这源自 DHA 对 EGFR 定位到细胞膜脂筏的完整性的抑制作用。由于 STAT3 和 NF-κB 的激活介导了生存基因 cyclin D1 和 survivin 的表达，因此 DHA 通过抑制 STAT3/NF-κB-cyclin D1/survivin 轴诱导细胞凋亡。这些结果支持了 DHA 通过破坏关键的促细胞生存信号通路诱导胰腺细胞凋亡的假说。我们建议，食用富含 DHA 的食物可以降低胰腺癌的发病率。
