Abstract
Background: Although it has been previously demonstrated that acute inflammation can promote the tumor growth of a sub-tumorigenic dose of melanoma cells through of 5-lipoxygenase inflammatory pathway and its product leukotriene B4, and also that the peritumoral treatment with eicosapentaenoic acid and its product, leukotriene B5, reduces the tumor development, the effect of the treatment by gavage with omega-3 and omega-6 in the tumor microenvironment favorable to melanoma growth associated with acute inflammation has never been studied. Methods: C57BL/6 mice were coinjected with 1 × 106 apoptotic cells plus 1 × 103 viable melanoma cells into the subcutaneous tissue and treated by gavage with omega-3-rich fish oil or omega-6-rich soybean oil or a mixture of these oils (1:1 ratio) during five consecutive days. Results: The treatment by gavage with a mixture of fish and soybean oils (1:1 ratio) both reduced the melanoma growth and the levels of leukotriene B4 (LTB4), prostaglandin E2 (PGE2), PGE2/prostaglandin E3 (PGE3) ratio, and CXC ligand 1 (CXCL1) and increased the levels of interleukin 10 (IL-10) to IL-10/CXCL1 ratio in the melanoma microenvironment. Conclusion: The oral administration of a 1:1 mixture of fish oil and soybean oil was able to alter the release of inflammatory mediators that are essential for a microenvironment favorable to the melanoma growth in mice, whereas fish oil or soybean oil alone was ineffective.
Highlights
Since Virchow described the presence of an intense leukocyte infiltration in tumors, the contribution of inflammatory factors to tumorigenesis and tumor progression became one of the main aspects studied in cancer
It has been demonstrated that neutrophils can be recruited from blood to tumor microenvironments by a variety of chemokines, such as CXC ligand 8 (CXCL8) or interleukin 8 (IL-8), growth-regulated oncogene alpha (GRO-α), and CXC ligand 1 (CXCL1), among others, and these cells can favor the tumor progression by releasing different types of cytokines, such as tumor necrosis factor alpha (TNF-α), interleukins (ILs) -1beta (1β), 6, 15, 17, and 18 [2]
Bachi et al [3] showed that the peritumoral treatment with eicosapentaenoic acid (EPA), as well as with leukotriene B5 (LTB5), the main mediator derived from EPA after 5-LOX activity, was able to reduce tumor growth in our experimental model
Summary
Since Virchow described the presence of an intense leukocyte infiltration in tumors, the contribution of inflammatory factors to tumorigenesis and tumor progression became one of the main aspects studied in cancer. Despite several studies that demonstrated how chronic inflammation contributes to the transformation, proliferation, and progression of many tumors, the effect of acute inflammation in tumor development is still poorly understood Regarding this fact, we have demonstrated that the acute inflammatory response is able to create favorable conditions to the tumor growth of a sub-tumorigenic dose of murine melanoma cells [3]. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two molecules derived from the alpha-linolenic acid metabolism, polyunsaturated fatty acid classified as omega-3, are targets of 5-LOX activity, and the mediators produce anti-inflammatory actions [5] Based on this information, Bachi et al [3] showed that the peritumoral treatment with EPA, as well as with leukotriene B5 (LTB5), the main mediator derived from EPA after 5-LOX activity, was able to reduce tumor growth in our experimental model. In order to gain insights into the effect of omega-3 and omega-6 in the growth of a sub-tumorigenic dose of melanoma cells dependent on an acute inflammatory response, in this study, mice were treated by gavage with omega-3-rich fish oil or omega-6-rich soybean oil, or a mixture of these oils in a ratio of 1:1, and the tumor growth, as well as the concentrations of inflammatory mediators (LTB4, LTB5, prostaglandin E2 (PGE2), and prostaglandin E3 (PGE3)) and cytokines (IL-6, IL-10, and CXCL1) in the tumor microenvironment, were evaluated
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