Int J Med Sci 2022; 19(14):2044-2057. doi:10.7150/ijms.75848 This issue Cite

Research Paper

Fish Oil and Selenium with Doxorubicin Modulates Expression of Fatty Acid Receptors and Selenoproteins, and Targets Multiple Anti-Cancer Signaling in Triple-negative Breast Cancer Tumors

Chih-Hung Guo1,2✉, Min-Yi Shih1,2, Chieh-Han Chung2, Yi-Chun Lin2, Ciou-Ting Fan2, Chia-Lin Peng2, Pei-Chung Chen2, Simon Hsia2✉

1. Micronutrition and Biomedical Nutrition Labs, Institute of Biomedical Nutrition, Hung-Kuang University, Taichung 433, Taiwan
2. Taiwan Nutraceutical Association, Taipei 105, Taiwan

Citation:
Guo CH, Shih MY, Chung CH, Lin YC, Fan CT, Peng CL, Chen PC, Hsia S. Fish Oil and Selenium with Doxorubicin Modulates Expression of Fatty Acid Receptors and Selenoproteins, and Targets Multiple Anti-Cancer Signaling in Triple-negative Breast Cancer Tumors. Int J Med Sci 2022; 19(14):2044-2057. doi:10.7150/ijms.75848. https://www.medsci.org/v19p2044.htm
Other styles

File import instruction

Abstract

Graphic abstract

Omega-3 fatty acids from fish oil (FO) and selenium (Se) potentiate some conventional therapies and have anticancer immune potential. This study aims to determine whether FO/Se modulates G-protein-coupled polyunsaturated fatty acid receptors (GPR-40 and GPR-120) and selenoproteins (Sel-H, Sel-W, and GPx4), and increases the therapeutic effect of doxorubicin in a dose-dependent manner on triple-negative breast cancer (TNBC) mouse. Mice were randomized into 5 groups (n = 7/group) and treated with physiological saline (control), low-dose doxorubicin, and doxorubicin in combination with low, medium, or high doses of FO/Se. The expression of signaling molecules in tumors was determined by measuring either mRNA or protein expression. Compared with doxorubicin alone, combination treatment resulted in lower tumor sizes and fewer overall metastasis, lower GPR-40 mRNA levels, and higher expression of all selenoproteins. Doxorubicin-FO/Se combination treatment decreased expression of membrane EGFR and FGFR, down-regulated downstream PI3K/AKT/mTOR, MAPK/ERK, and JAK2/c-Src/STAT3 signaling, increased tumor suppressor PTEN/TSC1/TSC2 expression and P53 activation, and suppressed oncogenic transcription factor expression. Dose-dependent inhibition of proliferation index Ki-67, cell cycle, and stem-cell-related markers were observed. Decreased immune check-points PD-L1/CTLA-4/Foxp3/CD86 and increased PD-1/CD28/IL-2 expression was also found. These observations suggest that the nutritional supplements FO/Se increase the chemotherapeutic efficacy of doxorubicin against TNBC by modulating GPR-40 and selenoprotein and targeting multiple signaling pathways in tumor tissues.

Keywords: Anticancer signaling, Doxorubicin, Fish oil and selenium, GPR-40, Immune microenvironment, Selenoproteins, TNBC mouse tumor


Citation styles

APA
Guo, C.H., Shih, M.Y., Chung, C.H., Lin, Y.C., Fan, C.T., Peng, C.L., Chen, P.C., Hsia, S. (2022). Fish Oil and Selenium with Doxorubicin Modulates Expression of Fatty Acid Receptors and Selenoproteins, and Targets Multiple Anti-Cancer Signaling in Triple-negative Breast Cancer Tumors. International Journal of Medical Sciences, 19(14), 2044-2057. https://doi.org/10.7150/ijms.75848.

ACS
Guo, C.H.; Shih, M.Y.; Chung, C.H.; Lin, Y.C.; Fan, C.T.; Peng, C.L.; Chen, P.C.; Hsia, S. Fish Oil and Selenium with Doxorubicin Modulates Expression of Fatty Acid Receptors and Selenoproteins, and Targets Multiple Anti-Cancer Signaling in Triple-negative Breast Cancer Tumors. Int. J. Med. Sci. 2022, 19 (14), 2044-2057. DOI: 10.7150/ijms.75848.

NLM
Guo CH, Shih MY, Chung CH, Lin YC, Fan CT, Peng CL, Chen PC, Hsia S. Fish Oil and Selenium with Doxorubicin Modulates Expression of Fatty Acid Receptors and Selenoproteins, and Targets Multiple Anti-Cancer Signaling in Triple-negative Breast Cancer Tumors. Int J Med Sci 2022; 19(14):2044-2057. doi:10.7150/ijms.75848. https://www.medsci.org/v19p2044.htm

CSE
Guo CH, Shih MY, Chung CH, Lin YC, Fan CT, Peng CL, Chen PC, Hsia S. 2022. Fish Oil and Selenium with Doxorubicin Modulates Expression of Fatty Acid Receptors and Selenoproteins, and Targets Multiple Anti-Cancer Signaling in Triple-negative Breast Cancer Tumors. Int J Med Sci. 19(14):2044-2057.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image