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. 2020 Dec 7;20(1):372.
doi: 10.1186/s12906-020-03160-7.

Krill oil extract inhibits the migration of human colorectal cancer cells and down-regulates EGFR signalling and PD-L1 expression

Abilasha G Jayathilake  1 , Margaret F Veale  1 , Rodney Brain Luwor  2 , Kulmira Nurgali  1   3   4 , Xiao Q Su  5
Affiliations

Krill oil extract inhibits the migration of human colorectal cancer cells and down-regulates EGFR signalling and PD-L1 expression

Abilasha G Jayathilake et al. BMC Complement Med Ther. .

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: EGFR; Human colorectal cancer cells; Krill oil extract; Migration; PD-L1.

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Conflict of interest statement

The authors declare that they have no competing interest.

Figures

Fig. 1
Fig. 1
A schematic diagram of the transwell model
Fig. 2
Fig. 2
Effects of FFAE of krill oil on the viability of CRC cells
Fig. 3
Fig. 3
Quantification of apoptosis following the treatment with FFAE of krill oil
Fig. 4
Fig. 4
Expression of EGFR and pEGFR in DLD-1 cells following the treatment with FFAE of krill oil
Fig. 5
Fig. 5
Expression of EGFR and pEGFR in HT-29 cells following the treatment with FFAE of krill oil
Fig. 6
Fig. 6
Expression of pERK 1/ 2 in CRC cells following the treatment with FFAE of krill oil
Fig. 7
Fig. 7
Expression of pAKT in CRC cells following the treatment with FFAE of krill oil
Fig. 8
Fig. 8
Expression of PDL-1 in CRC cells following the treatment with FFAE of krill oil
Fig. 9
Fig. 9
Schematic summary of the modulation of EGFR signalling pathway by the FFAE of krill oil in CRC cells
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