Document Type : Original Article

Authors

1 PhD Student of Exercise Physiology, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Mazandaran, Babolsar, Iran.

2 Full Professor, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Mazandaran, Babolsar, Iran.

Abstract

Background and Aim: It is believed that sports programs have minimal impact on pathological changes in the lung tissue exposed to smoking carcinogens. The aim of this study was to investigate the effects of twelve weeks submaximal swimming exercise on the expression of STAT3 in lung tissue of rats following the exposure to the carcinogen NNK. Materials and Methods: Forty-six Wistar rats (with the average weight of 105.84 ± 27.93g) were divided into five groups: A) exercise (E), B) exercise-NNK (EN), C) NNK (N), D) control (C) and E) Vehicle group (V) group. Exercise groups completed swimming submaximal exercises for twelve weeks, five days per week (Water flow 4-10 L/min, 25-60min). Rats in Vehicle group and NNK treatment group were respectively administered subcutaneous injections of distilled water and NNK (12.5mg/kg, once a week, 12 weeks). 48 hours after the last exercise, rats died and samples of their lung tissue were collected and stored in -70ᵒ.  STAT3 expressions were measured by Real time PCR-ABI method. One-way analysis of variance and Tukey post hoc test (P≤0.05) were used for data analysis. Results: There was a significant increase (p≤0.05) in the NNK group compared to E (P=0.001) and EN (P=0.002) groups in the STAT3 gene expression while there was no significant difference (P>0.05) between exercise groups with the control and saline groups. Conclusion: It seems that submaximal training can be used as a complementary therapy method along with other methods to prevent main factors leading to tumors.

Keywords

Coussens, L. M., & Werb, Z. (2002). Inflammation and cancer. Nature, 420(6917), 860-867.
Donatto, F. F., Neves, R. X., Rosa, F. O., Camargo, R. G., Ribeiro, H., Matos-Neto, E. M., & Seelaender, M. (2013). Resistance exercise modulates lipid plasma profile and cytokine content in the adipose tissue of tumour-bearing rats. Cytokine, 61(2), 426-432.
Fischer, C. P. (2006). Interleukin-6 in acute exercise and training: what is the biological relevance. Exercise Immunology Review, 12(6-33), 41.
Ge, G. Z., Xu, T. R., & Chen, C. (2015). Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms. Acta Biochimica Biophysica Sinica, 47(7), 477-487.
Halappanavar, S., Russell, M., Stampfli, M. R., Williams, A., & Yauk, C. L. (2009). Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke. BMC Medical Genomics, 2(1), 56.
Hecht, S. S. (2003). Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nature Reviews Cancer, 3(10), 733-744.
Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., & Forman, D. (2011). Global cancer statistics. CA: A Cancer Journal for Clinicians, 61(2), 69-90.
Jensen, W., Oechsle, K., Baumann, H. J., Mehnert, A., Klose, H., Bloch, W., … & Baumann, F. T. (2014). Effects of exercise training programs on physical performance and quality of life in patients with metastatic lung cancer undergoing palliative chemotherapy. Contemporary Clinical Trials, 37(1), 120-128.
Kruijsen-Jaarsma, M., Révész, D., Bierings, M. B., Buffart, L. M., & Takken, T. (2013). Effects of exercise on immune function in patients with cancer: a systematic review. Exercise Immunology Review, 19, 120-143.
Lao, Y., Yu, N., Kassie, F., Villalta, P. W., & Hecht, S. S. (2007). Formation and accumulation of pyridyloxobutyl
DNA adducts in F344 rats chronically treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and enantiomers of its metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. Chemical Research in Toxicology, 20(2), 235.
Leitzmann, M. F., Koebnick, C., Abnet, C. C., Freedman, N. D., Park, Y., Hollenbeck, A., … & Schatzkin, A. (2009). Prospective study of physical activity and lung cancer by histologic type in current, former, and never smokers. American Journal of Epidemiology, 169(5), 542-553.
Leu, C. M., Wong, F. H., Chang, C., Shiu-Feng, H., & Cheng-po, H. (2003). Interleukin-6 acts as an antiapoptotic  factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways. Oncogene, 22(49), 7809.
Iliopoulos, D., Hirsch, H. A., & Struhl, K. (2009). An epigenetic switch involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell, 139(4), 693-706.
Lunz, W., Peluzio, M. C. G., Dias, C. M. G. C., Moreira, A. P. B., & Natali, A. J. (2008). Long-term aerobic swimming training by rats reduces the number of aberrant crypt foci in 1, 2-dimethylhydrazine-induced colon cancer. Brazilian Journal of Medical and Biological Research, 41(11), 1000-1004.
Miller, A., Brooks, G. D., McLeod, L., Ruwanpura, S., & Jenkins, B. J. (2015). Differential involvement of gp130
signalling pathways in modulating tobacco carcinogen-induced lung tumourigenesis. Oncogene, 34(12), 1510-1519.
Mirdar, SH., Arab, A., Hedayati, M., & Hajizade, A. (2012). The effect of pregnant rat swimming on hypoxia-inducible factor-1α levels of neonatal lung. Tehran University of Medical Sciences, 69(12). [Persian]
Murakami, T., Takigawa, N., Ninomiya, T., Ochi, N.,& Yasugi, M. (2014). Effect of AZD1480 in an epidermal growth factor receptor-driven lung cancer model. Lung Cancer, 83(1), 30-36.
Ostrowski, K., Schjerling, P., & Pedersen, B. K. (2000). Physical activity and plasma interleukin-6 in humans–effect of intensity of exercise. European Journal of Applied Physiology, 83(6), 512-515.
Siveen, K. S., Sikka, S., Surana, R., Dai, X., Zhang, J.,& Kumar, A. (2014). Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer, 1845(2), 136-154.
Tartibian, B., & Ebrahimi Torkaman, B. (2016). Inflammatory markers and muscle damage indices response to intense exercise in healthy boys: relationship between the markers. Journal of Practical Studies of Biosciences in Sport, 4(8), 31-41. [Persian]
Vieira, R. P., Almeida-Oliveira, A. R., Aquino-Junior, J. C., Oliveira-Junior, M. C., Andrade-Sousa, A. S., Assumpcao-Neto, E., … & Oliveira, A. P. L. (2014). Aerobic Exercise Reduces Asthma Phenotype Through Modulation Of SOCS-JAK-STAT Signaling. American Journal of Respiratory and Critical Care Medicine (pp. A6480-A6480). American Thoracic Society.
Yu, H., Lee, H., Herrmann, A., Buettner, R., & Jove, R. (2014). Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nature Reviews Cancer, 14(11), 736-746.
Yu, Y. B., Liao, Y. W., Su, K. H., Chang, T. M., Shyue, S. K., Kou, Y. R.,&, Lee, T. S. (2012). Prior exercise training alleviates the lung inflammation induced by subsequent exposure to environmental cigarette smoke. Acta Physiologica, 205(4), 532-540.