EPA significantly improves anti‑EGFR targeted therapy by regulating miR‑378 expression in colorectal cancer

  • Authors:
    • Wen‑Hui Weng
    • Wai‑Hung Leung
    • Yeu Jye Pang
    • Li‑Wei Kuo
    • Hsi‑Hsien Hsu
  • View Affiliations

  • Published online on: September 5, 2018     https://doi.org/10.3892/ol.2018.9408
  • Pages: 6188-6194
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Abstract

It is known that colorectal cancer (CRC) cells containing mutations of the genes KRAS and BRAF are predominate mechanisms causing resistance to epidermal growth factor receptor (EGFR) inhibitors, and commonly exhibit a lower expression of microRNA‑378 (miR‑378) when compared with the wild type. In the present study, the aim was to determine the possible mechanism which associates miR‑378 with the mitogen‑activated protein kinase pathway, and to determine the efficiency of eicosapentaenoic acid ethyl ester (EPA) in its ability to restore sensitivity towards cetuximab, an EGFR inhibitor. The results demonstrated that a combined treatment of 40 µM EPA with 0.2 µM cetuximab can significantly suppress the cell growth in KRAS‑mutant and control wild‑type cells. Furthermore, the higher phosphorylated protein level of extracellular‑signal‑regulated kinase 1/2 was notable in KRAS EPA‑treated cells (P=0.006‑0.047) and resulted in significantly increased cell death; however, inconsistent results were indicated in EPA‑treated BRAF‑mutant cells, compared with the original cells (without treatment). KRAS‑mutant and wild‑type Caco‑2 cells treated with EPA exhibited increased cetuximab response rates, but these response rates were reduced in the BRAF‑mutant cells. In conclusion, upregulation of miR‑378 induced by EPA may result in the significant restoration of sensitivity to cetuximab in the KRAS‑mutant cells. The present data will contribute to a notable potential therapeutic solution for future clinical CRC treatments.
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November-2018
Volume 16 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Weng WH, Leung WH, Pang YJ, Kuo LW and Hsu HH: EPA significantly improves anti‑EGFR targeted therapy by regulating miR‑378 expression in colorectal cancer. Oncol Lett 16: 6188-6194, 2018
APA
Weng, W., Leung, W., Pang, Y.J., Kuo, L., & Hsu, H. (2018). EPA significantly improves anti‑EGFR targeted therapy by regulating miR‑378 expression in colorectal cancer. Oncology Letters, 16, 6188-6194. https://doi.org/10.3892/ol.2018.9408
MLA
Weng, W., Leung, W., Pang, Y. J., Kuo, L., Hsu, H."EPA significantly improves anti‑EGFR targeted therapy by regulating miR‑378 expression in colorectal cancer". Oncology Letters 16.5 (2018): 6188-6194.
Chicago
Weng, W., Leung, W., Pang, Y. J., Kuo, L., Hsu, H."EPA significantly improves anti‑EGFR targeted therapy by regulating miR‑378 expression in colorectal cancer". Oncology Letters 16, no. 5 (2018): 6188-6194. https://doi.org/10.3892/ol.2018.9408