Article ; Online: Effects of S-pindolol in mouse pancreatic and lung cancer cachexia models.
Journal of cachexia, sarcopenia and muscle
2023 Volume 14, Issue 3, Page(s) 1244–1248
Abstract: Background: It is known that S-pindolol attenuates muscle loss in animal models of cancer cachexia ... function, which is strongly compromised in cachectic animals.: Methods: Here, we tested 3 mg/kg/day of S ... LLC).: Results: Treatment of mice with 3 mg/kg/day of S-pindolol in KPC or LLC cancer cachexia ...
Abstract | Background: It is known that S-pindolol attenuates muscle loss in animal models of cancer cachexia and sarcopenia. In cancer cachexia, it also significantly reduced mortality and improved cardiac function, which is strongly compromised in cachectic animals. Methods: Here, we tested 3 mg/kg/day of S-pindolol in two murine cancer cachexia models: pancreatic cancer cachexia (KPC) and Lewis lung carcinoma (LLC). Results: Treatment of mice with 3 mg/kg/day of S-pindolol in KPC or LLC cancer cachexia models significantly attenuated the loss of body weight, including lean mass and muscle weights, leading to improved grip strength compared with placebo-treated mice. In the KPC model, treated mice lost less than half of the total weight lost by placebo (-0.9 ± 1.0 vs. -2.2 ± 1.4 g for S-pindolol and placebo, respectively, P < 0.05) and around a third of the lean mass lost by tumour-bearing controls (-0.4 ± 1.0 vs. -1.5 ± 1.5 g for S-pindolol and placebo, respectively, P < 0.05), whereas loss of fat mass was similar. In the LLC model, the gastrocnemius weight was higher in sham (108 ± 16 mg) and S-pindolol tumour-bearing (94 ± 15 mg) mice than that in placebo (83 ± 12 mg), whereas the soleus weight was only significantly higher in the S-pindolol-treated group (7.9 ± 1.7 mg) than that in placebo (6.5 ± 0.9). Grip strength was significantly improved by S-pindolol treatment (110.8 ± 16.2 vs. 93.9 ± 17.1 g for S-pindolol and placebo, respectively). A higher grip strength was observed in all groups; whereas S-pindolol-treated mice improved by 32.7 ± 18.5 g, tumour-bearing mice only show minimal improvements (7.3 ± 19.4 g, P < 0.01). Conclusions: S-pindolol is an important candidate for clinical development in the treatment of cancer cachexia that strongly attenuates loss of body weight and lean body mass. This was also seen in the weight of individual muscles and resulted in higher grip strength. |
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MeSH term(s) | Mice ; Animals ; Cachexia/drug therapy ; Cachexia/etiology ; Cachexia/pathology ; Lung Neoplasms/complications ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Muscle, Skeletal/pathology ; Carcinoma, Lewis Lung/complications ; Carcinoma, Lewis Lung/drug therapy ; Carcinoma, Lewis Lung/pathology ; Pancreas/pathology |
Language | English |
Publishing date | 2023-05-02 |
Publishing country | Germany |
Document type | Journal Article |
ZDB-ID | 2586864-0 |
ISSN | 2190-6009 ; 2190-5991 |
ISSN (online) | 2190-6009 |
ISSN | 2190-5991 |
DOI | 10.1002/jcsm.13249 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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