Abstract
The presence of a tumour is very often associated with wasting in the host, affecting both skeletal muscle and adipose tissue. In the present study we used sorafenib, a multi-kinase inhibitor with anti-tumour activity, in order to investigate the effects of chemotherapy on wasting. Three different experimental mouse tumour models were included: C26 colon carcinoma, B16 melanoma and Lewis lung carcinoma (LLC). The results obtained clearly show that sorafenib was effective in reducing tumour growth in LLC and B16 models, while it had no effect on C26. Interestingly, sorafenib treatment reduced the signs of muscle wasting and improved the physical activity in the LLC model and also in the C26, despite the absence of antineoplastic action in the latter. Our results discard a role for IL-6 in the action of sorafenib since the drug did not affect the levels of this cytokine. Conversely, sorafenib seems to act by influencing both STAT3 and ERK activity at muscle level, leading to reduced accumulation of Pax7 and atrogin-1. Sorafenib may interfere with muscle wasting by decreasing the activation of these signal transduction pathways.
Highlights
Development of cachexia is often found in cancer patients
tumour bearers (TB) animals were divided into two sub-groups: untreated (n58) and treated every day with sorafenib (90 mg/kg of initial body weight; n58)
In order to ascertain the effects of sorafenib on tumour-bearing animals we used three distinct experimental models: C26 colon carcinoma, B16 melanoma and Lewis lung carcinoma (LLC)
Summary
Development of cachexia is often found in cancer patients It occurs in 50 to 80% of these patients [1], and is considered as a predictor of reduced survival accounting for more than 20% of cancer patients deaths [2]. Inflammation, insulin resistance and increased muscle protein breakdown are frequently associated with cachexia. The metabolic disturbances found in the cancer patient include an increased energy inefficiency, insulin resistance and altered carbohydrate metabolism, adipose tissue dissolution and hypertriglyceridemia and muscle wasting. All of these alterations have a causative role in the development of the cachexia syndrome [7, 8]
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