Busquets Silvia, Castillejo Marta, Jové Queralt, Jude Baptiste, Mejías Patricia, López-Soriano Francisco J, Argilés Josep M
Cancer Research Group, Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain.
Onco Targets Ther. 2021 Mar 17;14:1953-1959. doi: 10.2147/OTT.S293834. eCollection 2021.
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.
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.
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.
It is concluded that, in the preclinical cachectic model used, no synergy exists between β2-agonist treatment and the blockade of sarcoplasmic-calcium flow.
在癌症恶病质期间，骨骼肌和脂肪组织均会流失。已证明使用β2激动剂，尤其是福莫特罗，在临床前模型中治疗该综合征非常成功。本研究的目的是研究福莫特罗与兰尼碱受体1（RyR1）抑制剂丹曲林联合使用对荷瘤动物体重减轻和恶病质的影响。
将大鼠分为两组：对照组（C）和荷瘤组（TB）。TB组进一步细分为四组：未治疗组（以生理盐水作为赋形剂）、福莫特罗治疗组（TF）（0.3mg/kg体重的生理盐水，皮下注射（s.c.），每日一次）、丹曲林治疗组（TD）（5mg/kg体重的生理盐水，皮下注射（s.c.），每日一次）以及福莫特罗和丹曲林联合治疗组（TFD）（福莫特罗0.3mg/kg体重，皮下注射（s.c.），每日一次；丹曲林5mg/kg体重；皮下注射（s.c.），每日一次）。肿瘤移植7天后，测定所有实验组的肌肉重量、握力和总身体活动量。
与先前研究一样，福莫特罗在减少肌肉重量减轻方面具有非常积极的作用，而丹曲林对骨骼肌和所研究的任何参数均无影响。最后，联合治疗（福莫特罗和丹曲林）并未对β2激动剂的作用产生任何显著益处。
得出的结论是，在所使用的临床前恶病质模型中，β2激动剂治疗与肌浆钙流阻断之间不存在协同作用。
