The Effect of an Incremental Swimming Training Period on CXCR4 Gene Expression in Lung Tissue in a Benzo[a]pyrene-Induced Lung Cancer Model in Balb/c Mice
Subject Areas : Journal of Physical Activity and HormonesRaheleh Kaka 1 , Elaheh Heidarnia 2 , Seyed Ali Hosseini 3
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Keywords: Swimming training, CXCR4, Lung cancer, Physical activity,
Abstract :
Introduction: Lung cancer is one of the most lethal malignancies, with smoking and air pollution being its primary risk factors. Early diagnosis and treatment improve survival rates. Studies suggest that inhibiting the CXC motif chemokine receptor type 4 (CXCR4) gene may offer a novel approach to controlling tumor growth and reducing metastasis. This study investigated the effects of incremental swimming training on CXCR4 expression in mice with benzo[a]pyrene (BZP)-induced lung cancer.
Material & Methods: In this experimental study, 12 male Balb/c mice (8–10 weeks old, 18–22 g) were induced with lung cancer via 100 mg/kg BZP injection and divided into two groups: a diseased control group (BZP) and a diseased + exercise group (BZP+ST). Six healthy mice served as the healthy control group (HC). The BZP+ST group underwent a 10-week swimming protocol (3 sessions/week), with durations gradually increasing from 15 to 40 minutes and carrying a load equivalent to 2% of their body weight. Data were analyzed using one-way ANOVA and Tukey’s post hoc test in SPSS v.22 (significance level: P ≤ 0.05).
Results: Final body weight was significantly lower in the BZP group compared to HC (P = 0.001), but improved in BZP+ST versus BZP (P = 0.001). CXCR4 expression was elevated in both BZP and BZP+ST groups compared to HC; however, swimming exercise led to a relative reduction in CXCR4 in the BZP+ST group versus BZP.
Conclusion: Incremental swimming training may suppress tumor growth and metastasis in lung cancer by downregulating CXCR4 expression and improving weight metrics. These findings highlight the potential of physical activity as an effective therapeutic strategy for lung cancer management, warranting further research.
1. Abekova A, Islamov R. ChemoProtective effects of new iodine coordinated compound in benzo [a] pyrene-induced lung cancer in BALB/c mice. In: BIO Web of Conferences. EDP Sciences; 2024. Vol. 100, p. 03001. doi: 10.1051/bioconf/202410003001
2. Adams SC, et al. The benefits of exercise in cancer patients: an overview. Curr Sports Med Rep. 2018;17(4):123-32. doi: 10.1249/JSR.0000000000000470
3. Argilés JM, Busquets S, Stemmler B, López-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14(11):754-62. doi: 10.1038/nrc3829
4. Baggish AL, Hale A, Weiner RB, Lewis GD, Systrom D, Wang F, et al. Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training. J Physiol. 2011;589(16):3983-94. doi: 10.1113/jphysiol.2011.213363
5. Bourke L, et al. Physical activity and exercise interventions for people with cancer: a systematic review. Cochrane Database Syst Rev. 2018;9:CD011007. doi: 10.1002/14651858.CD011007.pub2
6. Burger JA, Kipps TJ. CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood. 2006;107(5):1761-7. doi: 10.1182/blood-2005-08-3182
7. Coen PM, Goodpaster BH. Role of intramyocellular lipids in human health. Trends Endocrinol Metab. 2012;23(8):391-8. doi: 10.1016/j.tem.2012.05.009
8. Fahlman M, et al. Cardiovascular and respiratory responses of children to swimming training. Med Sci Sports Exerc. 2000;32(5):S209.
9. Fearon KC, Glass DJ, Guttridge DC. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab. 2012;16(2):153-66. doi: 10.1016/j.cmet.2012.06.011
10. Fei Z, Li D, Li K, Zhou M, Li Y, Li Y, et al. Detraining after tumor-bearing accelerates tumor growth while continuous training decreases tumor growth in mice. J Tradit Chin Med Sci. 2020;7(1):75-81. doi: 10.1016/j.jtcms.2020.01.007
11. Gonzalez JR, et al. Benzo[a]pyrene-induced lung cancer in mice. Cancer Lett. 2013;341(1):23-9. doi: 10.1016/j.canlet.2013.07.022
12. Gorr T, et al. Using Balb/c mice as a model for lung cancer research. Transl Lung Cancer Res. 2019;8(1):65-74. doi: 10.21037/tlcr.2018.12.06
13. Hardee JP, Counts BR, Carson JA. Understanding the role of exercise in cancer cachexia therapy. Am J Lifestyle Med. 2019;13(1):46-60. doi: 10.1177/1559827617725283
14. Hattori K, et al. Roles of chemokine receptor CXCR4 in cancer metastasis. Cancer Res. 2004;64(4):1001-5. doi: 10.1158/0008-5472.CAN-03-3198
15. Hojman P, Dethlefsen C, Brandt C, Hansen J, Pedersen L, Pedersen BK. Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth. Am J Physiol Endocrinol Metab. 2011;301(3):E504-10. doi: 10.1152/ajpendo.00520.2010
16. Javed R, Abbas T, Khan AH, Daud A, Bukhari A, Alharbey R. Deep learning for lungs cancer detection: a review. Artif Intell Rev. 2024;57(8):197. doi: 10.1007/s10462-024-10852-5
17. Mailing LJ, Allen JM, Buford TW, Fields CJ, Woods JA. Exercise and the gut microbiome: a review of the evidence, potential mechanisms, and implications for human health. Exerc Sport Sci Rev. 2019;47(2):75-85. doi: 10.1249/JES.0000000000000183
18. Mirdar Harijani S, Musavi N. The effect of 12 weeks of submaximal swimming training on immunoreactivity of Ras and Raf-1 in lung epithelial cells of Wistar rats exposed to carcinogen NN. Res Sport Med Technol. 2020;18(19):113-26.
19. Myrie L, et al. Exercise in lung cancer patients. Oncol Rep. 2019;41(2):711-20. doi: 10.3892/or.2018.6889
20. Paceli R, Cal R, Santos C, Morais A, Neiva C, Cordeiro A, et al. Anaerobic exercise decreases the progression of lung cancer in experimental mice.
21. Pedersen BK, Saltin B. Exercise as medicine – evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports. 2015;25(Suppl 3):1-72. doi: 10.1111/sms.12581
22. Radak Z. Exercise improves ROS/RNS balance in the liver of old rats. Free Radic Res. 2013;47(6-7):421-6. doi: 10.3109/10715762.2013.791022
23. Richardson PG, et al. Targeting CXCR4 in cancer therapy: the potential of CXCR4 inhibitors in treatment strategies. Clin Cancer Res. 2013;19(10):3234-43. doi: 10.1158/1078-0432.CCR-12-3603
24. Schmitz KH, et al. Physical activity and the risk of breast cancer: the role of physical activity in the treatment of breast cancer. Cancer Epidemiol Biomarkers Prev. 2010;19(10):2488-500. doi: 10.1158/1055-9965.EPI-10-0345
25. Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell. 2012;148(3):399-408. doi: 10.1016/j.cell.2012.01.021
26. Sharma R. Mapping of global, regional and national incidence, mortality and mortality-to-incidence ratio of lung cancer in 2020 and 2050. Int J Clin Oncol. 2022;27(4):665-75. doi: 10.1007/s10147-021-02086-7
27. Simpson RJ, Kunz H, Agha N, Graff R. Exercise and the regulation of immune functions. Prog Mol Biol Transl Sci. 2015;135:355-80. doi: 10.1016/bs.pmbts.2015.08.001
28. Sonveaux P. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells. In: Keystone symposium on Metabolism and Cancer Progression.
29. Spano JP, Andre F, Morat L, Sabatier L, Besse B, Combadiere C, et al. Chemokine receptor CXCR4 and early-stage non-small cell lung cancer: pattern of expression and correlation with outcome. Ann Oncol. 2004;15(4):613-7. doi: 10.1093/annonc/mdh136
30. Stanford KI, Goodyear LJ. Exercise and the regulation of adipose tissue metabolism. Prog Mol Biol Transl Sci. 2014;121:175-201. doi: 10.1016/B978-0-12-800101-1.00006-2
31. Torre LA, et al. Global cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7-30. doi: 10.3322/caac.21332
32. Zhan M, et al. CXCR4 expression and its role in lung cancer progression. J Cancer Res Clin Oncol. 2020;146(6):1449-63. doi: 10.1007/s00432-020-03215-6