The effect of resistance training on the expression relationship between IL-6 from skeletal muscle with Cathepsin B and FNDC5 from the hippocampus in rats with glioblastoma multiforme

Document Type : Original Article

Author

Department of Physical Education, Pardis Branch, Islamic Azad University, Pardis, Iran.

Abstract

Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with limited treatment options and a poor prognosis. In this study, we aimed to explore the potential effects of resistance training (RT) on the expression relationship between interleukin-6 (IL-6) from skeletal muscle and its interaction with Cathepsin B and Fibronectin type III domain-containing protein 5 (FNDC5) in the hippocampus of rats with GBM. To investigate the role of RT in GBM, we conducted a study using a rat model. By conducting a 4-week RT intervention (three days/week, 30 to 100% of body weight, 3 sets with 4 repetitions/session) and analyzing the expression levels of gastrocnemius muscle IL-6, hippocampal Cathepsin B, and FNDC5, we aimed to shed light on the potential impact of this RT modality on GBM progression. The results showed that GBM induced a significant decrease in gastrocnemius muscle IL-6, hippocampal FNDC5, and Cathepsin B gene expressions that were adjusted by RT. It means that there are significant increases in the GBM+RT group when compared to GBM. There were significant and positive correlations between variables (gastrocnemius muscle IL-6, hippocampal FNDC5, and hippocampal Cathepsin B gene expressions) which led to tissue crosstalk. In conclusion, this study contributes to our understanding of the molecular mechanisms associated with GBM, revealing potential avenues for future therapeutic interventions. RT may serve as a promising approach to modulate the expression relationship between IL-6, Cathepsin B, and FNDC5, offering a potential strategy for improving outcomes in GBM.

What is already known on this subject?

Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with limited treatment options and a poor prognosis.

 

What this study adds?

RT can reverse the GBM-induced decrease in the gene expressions of gastrocnemius muscle IL-6, and hippocampus FNDC5 and Cathepsin B.

Keywords

Main Subjects

Acknowledgements

None.

Funding

None.

Compliance with ethical standards

Conflict of interest The authors declare that they have no conflict of interest.

Ethical approval The study was approved by the Ethics Committee of the Islamic Azad University, Tehran, Iran (IR.IAU.SRB.REC.1401.029).

Informed consent Animal study.

Author contributions

Conceptualization: S.R.; Methodology: S.R.; Software: S.R.; Validation: S.R.; Formal analysis: S.R.; Investigation: S.R.; Resources: S.R.; Data curation: S.R.; Writing - original draft: S.R.; Writing - review & editing: S.R.; Visualization: S.R.; Supervision: S.R.; Project administration: S.R.; Funding acquisition: S.R.

References

Abou Sawan S, Nunes EA, Lim C, McKendry J, & Phillips SM. (2023). The Health Benefits of Resistance Exercise: Beyond Hypertrophy and Big Weights. Exercise, Sport, and Movement, 1(1).
Angom RS, Nakka NMR, & Bhattacharya S. (2023). Advances in Glioblastoma Therapy: An Update on Current Approaches. Brain Sci, 13(11). doi: https://doi.org/10.3390/brainsci13111536
Azimi Dokht SMA, Gharakhanlou R, Naghdi N, Khodadadi D, & Zare Zade Mehrizi AA. (2019). The effect of the treadmill running on genes expression ofthePGC-1α, FNDC5 and BDNF in hippocampus of male rats %J Journal of Practical Studies of Biosciences in Sport. 7(14), 91-101. doi: https://doi.org/10.22077/jpsbs.2017.1037.1321
Carson JA, & Baltgalvis KA. (2010). Interleukin 6 as a key regulator of muscle mass during cachexia. Exerc Sport Sci Rev, 38(4), 168-176. doi: https://doi.org/10.1097/JES.0b013e3181f44f11
Davis ME. (2016). Glioblastoma: Overview of Disease and Treatment. Clin J Oncol Nurs, 20(5 Suppl), S2-8. doi: https://doi.org/10.1188/16.Cjon.S1.2-8
Foo CY, Munir N, Kumaria A, Akhtar Q, Bullock CJ, Narayanan A, & Fu RZ. (2022). Medical Device Advances in the Treatment of Glioblastoma. Cancers (Basel), 14(21). doi: https://doi.org/10.3390/cancers14215341
Gondi CS, & Rao JS. (2013). Cathepsin B as a cancer target. Expert Opin Ther Targets, 17(3), 281-291. doi: https://doi.org/10.1517/14728222.2013.740461
Abou Sawan S, Nunes EA, Lim C, McKendry J, & Phillips SM. (2023). The Health Benefits of Resistance Exercise: Beyond Hypertrophy and Big Weights. Exercise, Sport, and Movement, 1(1).
Angom RS, Nakka NMR, & Bhattacharya S. (2023). Advances in Glioblastoma Therapy: An Update on Current Approaches. Brain Sci, 13(11). doi: https://doi.org/10.3390/brainsci13111536
Azimi Dokht SMA, Gharakhanlou R, Naghdi N, Khodadadi D, & Zare Zade Mehrizi AA. (2019). The effect of the treadmill running on genes expression ofthePGC-1α, FNDC5 and BDNF in hippocampus of male rats %J Journal of Practical Studies of Biosciences in Sport. 7(14), 91-101. doi: https://doi.org/10.22077/jpsbs.2017.1037.1321
Carson JA, & Baltgalvis KA. (2010). Interleukin 6 as a key regulator of muscle mass during cachexia. Exerc Sport Sci Rev, 38(4), 168-176. doi: https://doi.org/10.1097/JES.0b013e3181f44f11
Davis ME. (2016). Glioblastoma: Overview of Disease and Treatment. Clin J Oncol Nurs, 20(5 Suppl), S2-8. doi: https://doi.org/10.1188/16.Cjon.S1.2-8
Foo CY, Munir N, Kumaria A, Akhtar Q, Bullock CJ, Narayanan A, & Fu RZ. (2022). Medical Device Advances in the Treatment of Glioblastoma. Cancers (Basel), 14(21). doi: https://doi.org/10.3390/cancers14215341
Gondi CS, & Rao JS. (2013). Cathepsin B as a cancer target. Expert Opin Ther Targets, 17(3), 281-291. doi: https://doi.org/10.1517/14728222.2013.740461
Rašková M, Lacina L, Kejík Z, Venhauerová A, Skaličková M, Kolář M, . . . Brábek J. (2022). The Role of IL-6 in Cancer Cell Invasiveness and Metastasis-Overview and Therapeutic Opportunities. Cells, 11(22). doi: https://doi.org/10.3390/cells11223698
Ruiz-López E, Calatayud-Pérez J, Castells-Yus I, Gimeno-Peribáñez MJ, Mendoza-Calvo N, Morcillo M, & Schuhmacher AJ. (2021). Diagnosis of Glioblastoma by Immuno-Positron Emission Tomography. Cancers (Basel), 14(1). doi: https://doi.org/10.3390/cancers14010074
Seker-Polat F, Pinarbasi Degirmenci N, Solaroglu I, & Bagci-Onder T. (2022). Tumor Cell Infiltration into the Brain in Glioblastoma: From Mechanisms to Clinical Perspectives. Cancers (Basel), 14(2). doi: https://doi.org/10.3390/cancers14020443
Shirvani H, Rahmati-Ahmadabad S, Broom DR, & Mirnejad R. (2019). Eccentric resistance training and β-hydroxy-β-methylbutyrate free acid affects muscle PGC-1α expression and serum irisin, nesfatin-1 and resistin in rats. Journal of Experimental Biology, 222(10), jeb198424. doi: https://doi.org/10.1242/jeb.198424
Swanson LW. (2018). Brain maps 4.0—Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps. Journal of Comparative Neurology, 526(6), 935-943.
Wang J, Zheng M, Yang X, Zhou X, & Zhang S. (2023). The Role of Cathepsin B in Pathophysiologies of Non-tumor and Tumor tissues: A Systematic Review. J Cancer, 14(12), 2344-2358. doi: https://doi.org/10.7150/jca.86531
West AJ, Tsui V, Stylli SS, Nguyen HPT, Morokoff AP, Kaye AH, & Luwor RB. (2018). The role of interleukin-6-STAT3 signalling in glioblastoma. Oncol Lett, 16(4), 4095-4104. doi: https://doi.org/10.3892/ol.2018.9227
Wrann Christiane D, White James P, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, . . . Spiegelman Bruce M. (2013). Exercise Induces Hippocampal BDNF through a PGC-1α/FNDC5 Pathway. Cell Metabolism, 18(5), 649-659. doi: https://doi.org/10.1016/j.cmet.2013.09.008
Wu W, Klockow JL, Zhang M, Lafortune F, Chang E, Jin L, . . . Daldrup-Link HE. (2021). Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance. Pharmacol Res, 171, 105780. doi: https://doi.org/10.1016/j.phrs.2021.105780
Yadati T, Houben T, Bitorina A, & Shiri-Sverdlov R. (2020). The Ins and Outs of Cathepsins: Physiological Function and Role in Disease Management. Cells, 9(7). doi: https://doi.org/10.3390/cells9071679
Young MF, Valaris S, & Wrann CD. (2019). A role for FNDC5/Irisin in the beneficial effects of exercise on the brain and in neurodegenerative diseases. Prog Cardiovasc Dis, 62(2), 172-178. doi: https://doi.org/10.1016/j.pcad.2019.02.007
Zarezadehmehrizi A, Rajabi H, Gharakhanlou R, Naghdi N, & Azimidokht SMAJJoSSUoMS. (2019). Effect of 8 weeks of aerobic training on genes expression of hypoxia inducible factor HIF-1α, vascular endothelial growth factor (VEGF) and angiostatin in hippocampus of male rats with wistar model.
Zhao R. (2022). Irisin at the crossroads of inter-organ communications: Challenge and implications. Front Endocrinol (Lausanne), 13, 989135. doi: https://doi.org/10.3389/fendo.2022.989135
Journal of Exercise & Organ Cross Talk
Volume 3, Issue 4
December 2023
Pages 201-207

Files

History

  • Receive Date: 07 October 2023
  • Revise Date: 09 December 2023
  • Accept Date: 30 December 2023

Share

How to cite

Statistics