A Combination of Formoterol and the Histone Deacetylase Inhibitor AR42 has No Effects on Muscle Mass in Tumor-Bearing Rats

Silvia Busquets,Alina Noguera,Francisco J López-Soriano,Marta Castillejo,Josep M Argilés,Queralt Jove

doi:10.31487/j.ijcst.2021.02.02

Abstract

Background: Accelerated muscle and adipose tissue loss are two of the main aspects of cancer cachexia. β2-agonists seem to be successful in the treatment of cachexia in experimental animals. The aim if the present investigation was to study the effects on body weight loss in tumor-bearing animals of a combination of formoterol and AR-42, an inhibitor of histone deacetylase (HDAC). Methods: Rats were divided into two groups, namely controls (C) and tumor-bearing (T). TB group was further divided into four subgroups: untreated (saline as a vehicle), treated with Formoterol (F) (0,3 mg/kg body weight in saline, subcutaneous (s.c.), daily), treated with AR-42 (A) (20 mg/kg body weight in olive oil, intragastric (i.g.), only the last 4 days). and double-treated treated (TFA) with Formoterol (0,3 mg/kg body weight, subcutaneous (s.c.), daily) and AR-42 (20 mg/kg body weight in olive oil, intragastric (i.g.), only the last 4 days). 7 days after tumor transplantation, muscle weights, grip force and total physical activity were determined in all experimental groups. Results: The presence of the Yoshida AH-130 ascites hepatoma induced severe muscle wasting in rats. Treatment of the tumor-bearing animals with the beta2-agonist formoterol (0,3 mg/kg), resulted in a significant improvement in the cachectic state of the animals. Treatment of the tumor-bearing animals with AR42 did not result in any effects on muscle wasting in the cachectic rats. Furthermore, the combination of formoterol and AR42 showed no additional effects to those observed with just formoterol. Conclusion: The results presented question the previously described effects of AR42 on cancer cachexia, probably due to its effect on tumor growth.

Highlights

Accelerated muscle and adipose tissue loss are two of the main aspects of cancer cachexia. 2-agonists seem to be successful in the treatment of cachexia in experimental animals
TB group was further divided into four subgroups: untreated, treated with Formoterol (F) (0,3 mg/kg body weight in saline, subcutaneous (s.c.), daily), treated with AR-42 (A) (20 mg/kg body weight in olive oil, intragastric (i.g.), only the last 4 days). and double-treated treated (TFA) with Formoterol (0,3 mg/kg body weight, subcutaneous (s.c.), daily) and AR-42 (20 mg/kg body weight in olive oil, intragastric (i.g.), only the last 4 days). 7 days after tumor transplantation, muscle weights, grip force and total physical activity were determined in all experimental groups
The results presented question the previously described effects of AR42 on cancer cachexia, probably due to its effect on tumor growth

Summary

Introduction

Accelerated muscle and adipose tissue loss are two of the main aspects of cancer cachexia. 2-agonists seem to be successful in the treatment of cachexia in experimental animals. Treatment of the tumor-bearing animals with AR42 did not result in any effects on muscle wasting in the cachectic rats. Cachexia is a useful tool for survival prediction, being held responsible for more than 20% of the deaths of cancer patients [2] It is directly responsible for a reduction in physical activity and quality of life and decreases the efficacy and outcome of anticancer therapy [3,4,5]. Both adipose tissue and muscle weights are reduced during cancer cachexia; muscle wasting is the main event. The loss of body weight and muscle mass are directly involved with survival and the physical performance of the patient [6]

Methods

Results

Conclusion