Ratio of n6 to n-3 Fatty Acids in the Diet Affects Tumor Growth and Cachexia in Walker 256 Tumor-Bearing Rats

Abstract

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.

Glucose metabolism by lymphocytes, macrophages, and tumor cells from Walker 256 tumor‐bearing rats supplemented with fish oil for one generation

“…It was observed that chronic exposure (weaning to adulthood) to fish oil decreases Walker 256 tumor growth by 76%. Our finding corroborates previous studies also in vivo 11,26 and ex vivo. 27 The mechanisms by which FO inhibits tumor growth are not fully understood and was not investigated here but may occur through decreased cellular proliferation, 27 increased lipid peroxidation, 27 decreased eicosanoid production within the tumor, 10 reduced intracellular signaling, 10 and an altered host immune response, 13 among others.…”

The Role of Inflammation in Colon Cancer

“…Colon cancer xenograft studies showed consistent protective effects (40-60 % reduction in xenograft size) in mice supplemented with ω-3 PUFAs as compared to untreated mice (Boudreau et al 2001;Kato et al 2002;Calviello et al 2004). Similar beneficial results were reported from studies with CRC cell allograft tumors (Mund et al 2007;Cannizzo and Broitman 1989;Togni et al 2003;Pizato et al 2005). In spite of these encouraging data, no published studies yet have investigated the anti-neoplastic effect of u-3 PUFAs in patients with primary or metastatic CRC.…”

Polyunsaturated Fatty Acids, Ulcerative Colitis and Cancer Prevention

“…IBDs cause nutritional deficiencies, such as calorie and protein malnutrition, and deficiencies in vitamins, minerals and trace elements. This underscores the importance of nutritional therapy in their treatment (Ferguson et al 2007, Pizato et al 2005, Razack et al 2007. Malnutrition is common in these patients, and interventions through adequate nutritional therapy so as to restore the nutritional status have been associated with an improved recovery process involving the improvement of the immune system during periods of the exacerbation of the disease (Razack et al 2007).…”