Cancer-related weight loss is different from simple starvation, in which refeeding restores normal nutritional status. In cancer patients, tumor-associated metabolic abnormalities prevent restoration of muscle mass by nutrient provision. Consequently, cancer-related malnutrition can evolve to cancer cachexia due to interactions between pro-inflammatory cytokines and host metabolism. Therefore nutritional support must to have the aim to reduce inflammatory status. Polyunsaturated fatty acids (n-3) can modulate inflammation, reducing cytokine production. About this topic there are several, but contradictory, studies. Aim of this research was to evaluate: 1) on patients with lung cancer the effect of n-3 supplementation, determining oxidative status, pro-inflammatory cytokines, PGE2, nutritional status; 2) the effect of “in vitro” n-3 supplementation in a neoplastic cachexia model. The “in vivo” study was a randomized double-blind placebo-controlled trial. Daily supplementation with n-3 in n-3 group or placebo in control group was given for 66 days. At different times the following parameters were evaluated: C-reactive protein, pro-inflammatory cytokines, PGE2, glutathione, ROS, HNE; body weight; the n-3 content in plasma and erythrocytes to evaluate the adherence to treatment. The “in vitro” study evaluated the effect of n-3 on differentiation of muscle C2C12 cells grown in medium conditioned by human tumour lung cells A427. As regards patient study, it was evidenced that some inflammatory parameters in n-3 group did not change during the time, whereas they increased in control group; IL-6 and PGE2 decreased in n-3 group in comparison with control. Moreover, there was an improvement of oxidative status and body weight, and the level of n-3 increased in patients treated with these fatty acids, confirming the compliance to treatment. As regards “in vitro” experiments, medium conditioned by A427 prevented myotube formation in muscle C2C12 cells; by contrast, when A427 cells were grown in the presence of n-3 for 24 or 48 hours, their conditioned medium induced the differentiation of C2C12. Results from both “in vivo” and “in vitro” studies evidenced a beneficial effect of n-3 in reducing cachectic status.
Effect of n-3 polyunsaturated fatty acids on cachexia in advanced lung cancer: study “in vivo” and “in vitro”.
ORALDI, Manuela;MUZIO, Giuliana;CANUTO, Rosa Angela;MAGGIORA, Marina
2010-01-01
Abstract
Cancer-related weight loss is different from simple starvation, in which refeeding restores normal nutritional status. In cancer patients, tumor-associated metabolic abnormalities prevent restoration of muscle mass by nutrient provision. Consequently, cancer-related malnutrition can evolve to cancer cachexia due to interactions between pro-inflammatory cytokines and host metabolism. Therefore nutritional support must to have the aim to reduce inflammatory status. Polyunsaturated fatty acids (n-3) can modulate inflammation, reducing cytokine production. About this topic there are several, but contradictory, studies. Aim of this research was to evaluate: 1) on patients with lung cancer the effect of n-3 supplementation, determining oxidative status, pro-inflammatory cytokines, PGE2, nutritional status; 2) the effect of “in vitro” n-3 supplementation in a neoplastic cachexia model. The “in vivo” study was a randomized double-blind placebo-controlled trial. Daily supplementation with n-3 in n-3 group or placebo in control group was given for 66 days. At different times the following parameters were evaluated: C-reactive protein, pro-inflammatory cytokines, PGE2, glutathione, ROS, HNE; body weight; the n-3 content in plasma and erythrocytes to evaluate the adherence to treatment. The “in vitro” study evaluated the effect of n-3 on differentiation of muscle C2C12 cells grown in medium conditioned by human tumour lung cells A427. As regards patient study, it was evidenced that some inflammatory parameters in n-3 group did not change during the time, whereas they increased in control group; IL-6 and PGE2 decreased in n-3 group in comparison with control. Moreover, there was an improvement of oxidative status and body weight, and the level of n-3 increased in patients treated with these fatty acids, confirming the compliance to treatment. As regards “in vitro” experiments, medium conditioned by A427 prevented myotube formation in muscle C2C12 cells; by contrast, when A427 cells were grown in the presence of n-3 for 24 or 48 hours, their conditioned medium induced the differentiation of C2C12. Results from both “in vivo” and “in vitro” studies evidenced a beneficial effect of n-3 in reducing cachectic status.
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