Fish oil attenuates surgery-induced immunosuppression, limits post-operative metastatic dissemination and increases long-term recurrence-free survival in rodents inoculated with cancer cells

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• 作者：Yael Goldfarb^a ; Haim Shapiro^b ; ^c ; Pierre Singer^b ; ^d ; ^e ; ^{psinger@clalit.org.il} ; Yael Kalderon^a ; Ben Levi^a ; Ariella Glasner^a ; Marganit Benish^a ; Shamgar Ben-Eliyahu^a
• 关键词：Peri-operative care ; Neoplasm metastasis ; Natural killer cells ; Omega-3 fatty acids ; Fish oil
• 刊名：Clinical Nutrition
• 出版年：2012
• 出版时间：June, 2012
• 年：2012
• 卷：31
• 期：3
• 页码：396-404
• 全文大小：529 K

文摘

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Summary

Background & aims

Omega-3 fatty acids (¦Ø-3FA) attenuate postoperative immunosuppression vis-¨¤-vis infection. Since immune-surveillance targets metastasizing cancer cells, we assessed the effect of ¦Ø-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, ¦Ø-3FA-enriched, or ¦Ø-6FA-enriched chow, beginning one week before subcutaneous footpad implantation of syngeneic melanoma cells. When tumors reached the volume of 110?¦Ìl, the tumor-bearing footpad was amputated, and long-term recurrence-free survival was assessed. Also, F344 rats were fed ¦Ø-3FA or ¦Ø-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

¦Ø-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 ¦Ø-3FA had large beneficial effects in non-operated rats and an even greater impact in operated rats.

Conclusions

¦Ø-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 ¦Ø-3FA-based nutrition in patients undergoing resection of a primary tumor.