Background & aims: Omega-3 fatty acids (ω-3FA) attenuate postoperative immunosuppression vis-à-vis infection. Since immune-surveillance targets metastasizing cancer cells, we assessed the effect of ω-3FA consumption on 1) early post-operative Natural Killer cell (NK) cytotoxicity and metastases and 2) long-term recurrence-free survival, in two rodent models of surgery-promoted metastases. Methods: C57BL/6J mice were fed standard, ω-3FA-enriched, or ω-6FA-enriched chow, beginning one week before subcutaneous footpad implantation of syngeneic melanoma cells. When tumors reached the volume of 110 μl, the tumor-bearing footpad was amputated, and long-term recurrence-free survival was assessed. Also, F344 rats were fed ω-3FA or ω-6FA for a month before undergoing or not undergoing laparotomy, and were intravenously inoculated with radio-labeled syngeneic adenocarcinoma cells. Marginating-pulmonary (MP)-leukocytes were harvested, and lung tumor retention (LTR) of metastases was assessed. Results: ω-3FA consumption did not affect the growth of footpad tumors, but significantly enhanced post-amputation recurrence-free survival in mice. Surgery had a deleterious effect on NK cell activity and LTR whereas ω-3FA had large beneficial effects in non-operated rats and an even greater impact in operated rats. Conclusions: ω-3FA feeding attenuates or even overcomes postoperative NK cell suppression, increases resistance to experimental and spontaneous metastasis, and enhances recurrence-free survival following excision of metastasizing primary tumors. These findings warrant clinical studies of ω-3FA-based nutrition in patients undergoing resection of a primary tumor.
Bibliographical noteFunding Information:
The authors are grateful for the excellent editorial assistance provided by Dr. Alexandra Mahler.The authors’ responsibilities were as follows – YG: managed all aspects of the survival and re-challenge studies, including the conduct and design of the experiments, data analysis and interpretation, and participated in the writing of the manuscript. YK: managed all aspects of the ex vivo rat study, including design and data interpretation, and participated in writing the manuscript. BL, AG, and MB aided in conducting both the survival and the rat study and assisted in FACS data analysis and interpretation. HS, PS, and SBE contributed to the concept and design of the experiments, data analysis, and to the writing of the manuscript. All authors critically reviewed, read and approved the manuscript.Sources of support: This work was supported by NIH/NCI grant # CA125456 (SBE).
- Fish oil
- Natural killer cells
- Neoplasm metastasis
- Omega-3 fatty acids
- Peri-operative care
ASJC Scopus subject areas
- Nutrition and Dietetics
- Critical Care and Intensive Care Medicine