Institute for Health and Sport, Victoria University, P.O. Box 14428, Melbourne, Vic, 8001, Australia.
Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.
BMC Complement Med Ther. 2020 Dec 7;20(1):372. doi: 10.1186/s12906-020-03160-7.
The currently available treatments for colorectal cancer (CRC) are often associated with serious side-effects. Therefore, the development of a novel nutraceutical agent may provide an alternative complementary therapy for CRC. Overexpression of the epidermal growth factor receptor (EGFR) associates with a range of cancers while downregulation of EGFR signalling can inhibit cancer growth. Our previous studies have shown that the free fatty acid extract (FFAE) of krill oil exhibits anti-proliferative and pro-apoptotic properties. This study determines the effects of krill oil extract on the migration of human CRC cells, and its potential role in modulating EGFR signalling pathway and the expression of programmed death ligand 1 (PD-L1).
Human CRC cells, DLD-1 and HT-29 were treated with FFAE of KO at 0.03 and 0.12 μL/100 μL for 8 or 24 h. Cell migration was determined by Boyden chamber migration assay. The expression of EGFR, phosphorylated EGFR (pEGFR), protein kinase B (AKT), phosphorylated AKT (pAKT), extracellular signal regulated kinase (ERK1/2), phosphorylated ERK1/2 (pERK1/2) as well as PD-L1 were assessed by western blotting and immunohistochemistry.
The FFAE of krill oil significantly inhibited cell migration compared to ethanol-treated (vehicle control) cells (P < 0.01 to P < 0.001). At the molecular level, krill oil extract reduced the expression of EGFR, pEGFR (P < 0.001 for both) and their downstream signalling, pERK1/2 and pAKT (P < 0.01 to P < 0.001) without altering total ERK 1/2 and AKT levels. In addition, the expression of PD-L1 was reduced by 67 to 72% (P < 0.001) following the treatment with krill oil extract.
This study has demonstrated that krill oil may be a potential therapeutic/adjunctive agent for CRC attributed to its anti-migratory effects.. The potential anti-cancer properties of krill oil are likely to be associated with the downregulation of EGFR, pEGFR and their downstream pERK/ERK1/2 and pAKT/AKT signalling pathways along with the downregulation of PD-L1.
目前用于结直肠癌（CRC）的治疗方法常伴有严重的副作用。因此，开发一种新的营养药物可能为 CRC 提供一种替代的补充治疗方法。表皮生长因子受体（EGFR）的过度表达与多种癌症有关，而 EGFR 信号的下调可以抑制癌症的生长。我们之前的研究表明，磷虾油的游离脂肪酸提取物（FFAE）具有抗增殖和促凋亡作用。本研究旨在确定磷虾油提取物对人 CRC 细胞迁移的影响，及其在调节 EGFR 信号通路和程序性死亡配体 1（PD-L1）表达中的潜在作用。
用 0.03 和 0.12μL/100μL 的磷虾油 FFAE 处理人 CRC 细胞 DLD-1 和 HT-29，分别处理 8 或 24 小时。通过 Boyden 室迁移实验测定细胞迁移。用 Western blot 和免疫组化法检测 EGFR、磷酸化 EGFR（pEGFR）、蛋白激酶 B（AKT）、磷酸化 AKT（pAKT）、细胞外信号调节激酶（ERK1/2）、磷酸化 ERK1/2（pERK1/2）以及 PD-L1 的表达。
与乙醇处理（溶剂对照）的细胞相比，磷虾油 FFAE 显著抑制细胞迁移（P<0.01 至 P<0.001）。在分子水平上，磷虾油提取物降低了 EGFR、pEGFR 的表达（均 P<0.001）及其下游信号 pERK1/2 和 pAKT（P<0.01 至 P<0.001），而总 ERK1/2 和 AKT 水平没有改变。此外，磷虾油提取物处理后 PD-L1 的表达降低了 67%至 72%（P<0.001）。
本研究表明，磷虾油可能因其抗迁移作用而成为 CRC 的一种潜在治疗/辅助药物。磷虾油的潜在抗癌特性可能与 EGFR、pEGFR 及其下游 pERK/ERK1/2 和 pAKT/AKT 信号通路的下调以及 PD-L1 的下调有关。
