Abstract
BackgroundCancer cachexia is a cancer-induced multifactorial debilitating syndrome directly accounting for 20% of cancer deaths without effective therapeutic approaches. It is extremely urgent to explore effective anti-cachexia drugs to ameliorate muscle and fat loss in cachexia patients.MethodsLewis lung carcinoma bearing C57BL/6 mice were applied as the animal model to examine the therapeutic effect of Coix seed oil (CSO) on cancer cachexia. The food intake and body weight change were monitored every 3 days throughout the experiment. The IL-6 and TNF-α levels in serum were detected by ELISA assay. Several key proteins involved in muscle wasting and fat lipolysis were tested by Western blot to identify the potential mechanism of CSO.ResultsAdministration of CSO through gavage significantly prevented body weight loss and ameliorated systemic inflammation without affecting food intake and tumor size. The weight and histological morphology of gastrocnemius muscle and epididymal adipose tissue in CSO-treated mice were also improved. In mechanism, we found that CSO decreased the expression of MuRF1 and the ratio of phospho-p65 (Ser536) to p65 in muscle tissue. Meanwhile, cancer-induced activation of HSL and AMPK was also inhibited by CSO administration.ConclusionCoix seed oil exerts an anti-cachexia pharmaceutical effect by counteracting muscle and adipose tissue loss most likely through regulating NF-κB-MuRF1 and AMPK-HSL pathway.
Highlights
Cancer cachexia is a cancer-induced multifactorial debilitating syndrome directly accounting for 20% of cancer deaths without effective therapeutic approaches
C57BL/6 mice were randomly assigned into three groups (7 mice per group): 1) control mice (Ctrl group) injected subcutaneously with phosphate buffer saline (PBS) in the right flank of axilla; 2) cachectic mice (CA group) injected subcutaneously with 1 × 106 Lewis lung carcinoma (LLC) cells in the right flank of axilla receiving daily gavage of 2.5 ml/kg sterile water; 3) cachectic mice treated with daily gavage of 2.5 ml/kg Coix seed oil (CA + Coix group)
The tumor-free body weight between these two groups showed a significant difference (Fig. 1d). These results demonstrated that Coix seed oil (CSO) administration attenuated BW loss of LLC bearing mice
Summary
Cancer cachexia is a cancer-induced multifactorial debilitating syndrome directly accounting for 20% of cancer deaths without effective therapeutic approaches. It is extremely urgent to explore effective anti-cachexia drugs to ameliorate muscle and fat loss in cachexia patients. Cancer cachexia is a devastating multifactorial disorder characterized by clinical symptoms of fatigue, anorexia and ongoing body weight (BW) loss [1]. It occurs in more than half of cancer patients, leading to reduced therapeutic efficacy, worse treatment tolerance, poor quality of life and prognosis [2, 3]. Skeletal muscle wasting is the most prominent feature of cachexia in cancer patients. The increased free fatty acids in blood circulation caused by lipolysis could excessively
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