BACKGROUND: Cancer cachexia is associated with catabolic conditions that trigger skeletal muscle wasting. Research has indicated the presence of sex differences in the development of cancer cachexia and in the severity of muscle mass loss. In male mice, the p38 mitogen-activated protein kinases (MAPK) are known to play a role in the progression of cancer cachexia. However, their role in female mice remains unclear. This study aimed to investigate whether there are alterations in p38 MAPK activity in female mice with cachexia. METHODS: Female ApcMin/+ (Min, n=4) mice and age-matched wild-type (WT, n=4) mice were used. The body weights were recorded every week. All the mice were sacrificed at 22 weeks old. Theright gastrocnemius (GAS) muscles were removed, weighed, and snap-frozen at sacrifice. The tissues were homogenized for routine western blotting using 30~50 µg of the total protein. Student's t-test was used to compare the difference between WT and Min. The coefficient of determination (r^2) was used to examine a significant correlation. The significance level was set at p<0.05. RESULTS: Female Min mice had smaller body weight (BW, 22.6 ± 0.3 g vs. 18.3 ± 1.7 g, for WT and Min mice, respectively, p<0.05). Min mice lost 18.9% of BW compared to their peak BW. Likewise, GAS weight in Min mice was smaller than in WT mice (104.2 ± 4.9 mg vs. 80.8 ± 9.4 mg, respectively). Western blot analysis showed that Min mice had a reduced phosphorylated state of eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) than WT mice by 34% (p< 0.05). Conversely, the levels of p38 MAPK activity were elevated in Min mice by 63% (p< 0.05). There was a significant correlation between 4E-BP1 and p38 MAPK (r^2=0.6609, p<0.05).CONCLUSIONS: These results suggest that p38 MAPK might contribute to muscle wasting by attenuating an anabolic pathway in female cachectic mice.

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