Decreased tumor growth in Walker 256 tumor-bearing rats chronically supplemented with fish oil involves COX-2 and PGE2 reduction associated with apoptosis and increased peroxidation.

Many studies have shown that addition of fish oil (FO) to the diet reduces tumor growth but the mechanism(s) of action involved is (are) still unknown. In this study, we examine some possible mechanisms in tumor-bearing rats chronically supplemented with FO. Male Wistar rats (21 days old) were fed with regular chow and supplemented with coconut or FO (1g/kg body weight) until they reached 70 days of age. Then, they were inoculated with a suspension of Walker 256 ascitic tumor cells (2 x 10(7)ml) and after 14 days they were killed. Supplementation with FO resulted in significantly lower tumor weight, greater tumor cell apoptosis, lower ex vivo tumor cell proliferation, a higher tumor content of lipid peroxides, lower expression of cyclooxygenase-2 (COX-2) in tumor tissue and a lower plasma concentration of prostaglandin E2 than observed in rats fed regular chow or supplemented with coconut oil. These results suggest that reduction of tumor growth by FO involves an increase in apoptosis and of lipid peroxidation in tumor tissue, with a reduction in tumor cell proliferation ex vivo, COX-2 expression and PGE2 production. Thus, FO may act simultaneously through multiple effects to reduce tumor growth. Whether these effects are connected through a single underlying mechanism remains to be seen.

Ratio of n6 to n-3 fatty acids in the diet affects tumor growth and cachexia in Walker 256 tumor-bearing rats.

In this study we investigate the impact of the dietary ratio of n-6 to n-3 fatty acids (FAs) from postweaning until adult age upon tumor growth, lipid peroxidation in tumor tissue, and metabolic indicators of cancer cachexia in Walker 256 tumor-bearing rats. Weanling male Wistar rats received a normal low-fat (40 g/kg diet) chow diet or high-fat diets (300 g/kg) that included fish oil (FO) or sunflower oil or blends of FO and sunflower oil to yield n-6 to n-3 FA ratios of approximately 6:1, 30:1, and 60:1 ad libitum. After 8 wk, half of each group was inoculated with 1 ml of 2 x 10(7) Walker 256 cells. At the 14th day after tumor inoculation, the animals were killed, and tumors and blood were removed. The different diets did not modify the blood parameters in the absence of tumor bearing, except the high-FO diet, which decreased serum cholesterol and triacylglycerol concentrations. Tumor weight in chow-fed rats was 19 g, and these rats displayed cancer cachexia, characterized by hypoglycemia, hyperlacticidemia, hypertriacylglycerolemia, loss of body weight, and food intake reduction. Tumor weight in FO-fed rats was 7.7 g, and these animals gained body weight (14.6 g) and maintained blood metabolic parameters similar to non-tumor-bearing animals. Tumor weight in rats fed the diet with an n-6 to n-3 FA ratio of 6:1 was similar to tumor-bearing, chow-fed rats, but they gained 2 g in the body weight and blood metabolic parameters were similar to those in non-tumor-bearing rats. However, a further increase in the n-6 FA content of the diet did not change the cachectic state associated with tumor bearing. In this experimental model, a dietary n-6 to n-3 FA ratio of 6:1 was able to increase food intake and body weight, restore the biochemical blood parameters of cachexia, and prevent the development of cancer cachexia.