Lack of Synergy Between β-Agonist Treatment and a Blockage of Sarcoplasmic Calcium Flow in a Rat Cancer Cachexia Model

Silvia Busquets; Marta Castillejo; Queralt Jové; Baptiste Jude; Patricia Mejías; Francisco J López-Soriano; Josep M Argilés

doi:10.2147/OTT.S293834

Lack of Synergy Between β-Agonist Treatment and a Blockage of Sarcoplasmic Calcium Flow in a Rat Cancer Cachexia Model

Onco Targets Ther. 2021 Mar 17:14:1953-1959. doi: 10.2147/OTT.S293834. eCollection 2021.

Authors

Silvia Busquets^{1

2}, Marta Castillejo¹, Queralt Jové¹, Baptiste Jude³, Patricia Mejías¹, Francisco J López-Soriano^{1

2}, Josep M Argilés^{1

2}

Affiliations

¹ Cancer Research Group, Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
² Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain.
³ Laboratoire de Physiologie - EA 4324 ORPHY, IBSAM, Université de Bretagne Occidentale, Brest, France.

Abstract

Background: During cancer cachexia, both skeletal muscle and adipose tissue losses take place. The use of β2-agonists, formoterol in particular, has proven to be very successful in the treatment of the syndrome in pre-clinical models. The object of the present research was to study the effects of a combination of formoterol and dantrolene, an inhibitor of the ryanodine receptor 1 (RyR1), on body weight loss and cachexia in tumour-bearing animals.

Methods: Rats were separated into two groups: controls (C) and tumour bearing (TB). TB group was further subdivided into four groups: untreated (saline as a vehicle), treated with Formoterol (TF) (0,3 mg/kg body weight in saline, subcutaneous (s.c.), daily), treated with Dantrolene (TD) (5 mg/kg body weight in saline, subcutaneous (s.c.), daily), and double-treated treated (TFD) with Formoterol (0,3 mg/kg body weight, subcutaneous (s.c.), daily) and Dantrolene (5 mg/kg body weight, subcutaneous (s.c.), daily). 7 days after tumour transplantation, muscle weight, grip force, and total physical activity were specified in all experimental groups.

Results: While formoterol had, as in previous studies, a very positive effect in reducing muscle weight loss, dantrolene had no effects, neither on skeletal muscle nor on any of the parameters studied. Finally, the combined treatment (formoterol and dantrolene) did not result in any significant benefit on the action of the β2-agonist.

Conclusion: It is concluded that, in the preclinical cachectic model used, no synergy exists between β2-agonist treatment and the blockade of sarcoplasmic-calcium flow.

Keywords: calcium; cancer cachexia; dantrolene; formoterol; ryanodine receptor 1; skeletal muscle.

Grants and funding

This work was supported by a grant from the Ministerio de Economia y Competitividad (SAF2015-65589-P), this funding supported the design of the study, analysis and interpretation of data.