Aerobic training affects the expression of oncogenic genes in prostate tissue in male rats
الموضوعات : Sport Physiology
Hossein Manzouri
1
,
Mohammad Ali Azarbayjani
2
,
Hasan Matinhomaee
3
1 - Department of Physical Education and Sport Sciences, CT.C., Islamic Azad University, Tehran, Iran.
2 - Department of Physical Education and Sport Sciences, CT.C., Islamic Azad University, Tehran, Iran.
3 - Department of Physical Education and Sport Sciences, CT.C., Islamic Azad University, Tehran, Iran.
الکلمات المفتاحية: Aerobic training, prostate cancer, MMP2, MMP9,
ملخص المقالة :
Since the effect of aerobic training on MMP-9 and MMP-2 gene expression in prostate tissue under cancer conditions is unknown, the present study was conducted to establish the effect of aerobic training on MMP-9 and MMP-2 gene expression in prostate tissue of male rats. In an experimental study, 30 male Wistar rats were randomly divided into 3 groups: 1-control-healthy group, 2-control-prostate cancer group, and 3-prostate cancer-aerobic training group. After prostate cancer was induced using LNCaP and TSP-1-EnSC cell lines, the subjects underwent aerobic training for eight weeks. After prostate cancer was induced using LNCaP and TSP-1-EnSC cell lines, the subjects underwent aerobic training for eight weeks. At the end of the eighth week, the rats were sacrificed and their prostate tissue was removed. This was done to measure MMP-9 and MMP-2 gene expression by Real Time PCR. The results showed that MMP-9 gene expression (P=0.006) was considerably higher in the control-prostate cancer induction group than in the control-healthy group. MMP-9 gene expression (P=0.009) was significantly lower in the prostate cancer-aerobic training group than in the control prostate cancer group. MMP-2 gene expression (P=0.006) was significantly lower in the prostate cancer-aerobic training group than in the control prostate cancer induction group. The results of the present study show that prostate cancer induction is associated with increased expression of MMP-2 and MMP-9 genes, known as oncogenic genes. Aerobic training reduces the expression of MMP-9 and MMP-2 genes, which indicates that aerobic training in induced prostate cancer can prevent prostate tumor development by inhibiting the expression of oncogenic genes, so it is recommended to use aerobic training in prostate cancer conditions.
1-American Cancer Society. Cancer Facts & Figures 2009. Atlanta: American Cancer Society, 2009
2- Zhu S, He J, Yin L, Zhou J, Lian J, Ren Y, Zhang X, Yuan J, Wang G, Li X. Matrix metalloproteinases targeting in prostate cancer. Urol Oncol. 2024 Sep;42(9):275-287.
Brehmer B, Biesterfeld S, Jakse G. Expression of matrix metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and -2) in prostate cancer tissue. Prostate Cancer Prostatic Dis. 2003;6(3):217-22.
3-Andersen MF, Midtgaard J, Bjerre ED. Do Patients with Prostate Cancer Benefit from Exercise Interventions? A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2022 Jan 15;19(2):972.
4-Giganti MG, Tresoldi I, Sorge R, Melchiorri G, Triossi T, Masuelli L, Lido P, Albonici L, Foti C, Modesti A, Bei R. Physical exercise modulates the level of serum MMP-2 and MMP-9 in patients with breast cancer. Oncol Lett. 2016 Sep;12(3):2119-2126.
5- Attar Shakri, Hossein, Fattahi, Esmail, Nowrozi, Mohammad Reza, Momeni, Seyed Ali, Piriaei, Abbas. Investigating the combined effect of endostatin with endometrial stem cells expressing the anti-angiogenic gene TSP-1 on angiogenesis-inducing factors in the treatment of rat prostate cancer. Animal Biology Quarterly, 2019; 13(2): 101-114.
6- McCullough, Danielle J. Linda M.-D. Nguyen, Dietmar W. Siemann, and Bradley J. Behnke. Effects of exercise training on tumor hypoxia and vascular function in the rodent preclinical orthotopic prostate cancer model. Journal of Applied Physiology 2013 115:12, 1846-1854
7- Gialeli C, Theocharis AD, Karamanos NK. Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. FEBS J. 2011(278):16–27.
8-Ye H, He Y, Wang J, Song T, Lan Z, Zhao Y, Xi M. Effect of matrix metalloproteinase promoter polymorphisms on endometriosis and adenomyosis risk: evidence from a meta-analysis. J Genet. 2016;95:611–19.
9-Brown GT, Murray GI. Current mechanistic insights into the roles of matrix metalloproteinases in tumour invasion and metastasis. J Pathol. 2015(237):273–281.
10-Xu W, Xu H, Fang M, Wu X, Xu Y. MKL1 links epigenetic activation of MMP2 to ovarian cancer cell migration and invasion. Biochem Biophys Res Commun. 2017;487:500–08.
11-Ding X, Yang DR, Xia L, Chen B, Yu S, Niu Y, Wang M, Li G, Chang C. Targeting TR4 nuclear receptor suppresses prostate cancer invasion via reduction of infiltrating macrophages with alteration of the TIMP-1/MMP2/MMP9 signals. Mol Cancer. 2015;14:16.
12-Moroz A, Delella FK, Almeida R, Lacorte LM, Fávaro WJ, Deffune E, Felisbino SL. Finasteride inhibits human prostate cancer cell invasion through MMP2 and MMP9 downregulation. PLoS One. 2013;8:e84757.
13-Lu S, Zhu Q, Zhang Y, Song W, Wilson MJ, Liu P. Dual-Functions of miR-373 and miR-520c by Differently Regulating the Activities of MMP2 and MMP9. J Cell Physiol. 2015;230:1862–70.
14-Liao X, Thrasher JB, Pelling J, Holzbeierlein J, Sang QX, Li B. Androgen stimulates matrix metalloproteinase-2 expression in human prostate cancer. Endocrinology. 2003 May;144(5):1656-63.
15-Al-Rashidi RR, Noraldeen SAM, Kareem AK, Mahmoud AK, Kadhum WR, Ramírez-Coronel AA, Iswanto AH, Obaid RF, Jalil AT, Mustafa YF, Nabavi N, Wang Y, Wang L. Malignant function of nuclear factor-kappaB axis in prostate cancer: Molecular interactions and regulation by non-coding RNAs. Pharmacol Res. 2023 Aug;194:106775.
16-Dai Y, Bae K, Siemann DW. Impact of hypoxia on the metastatic potential of human prostate cancer cells. Int J Radiat Oncol Biol Phys. 2011 Oct 1;81(2):521-8.
17-Aalinkeel R, Nair BB, Reynolds JL, Sykes DE, Mahajan SD, Chadha KC, Schwartz SA. Overexpression of MMP-9 contributes to invasiveness of prostate cancer cell line LNCaP. Immunol Invest. 2011;40(5):447-64.
18-Gong Y., Chippada-Venkata U.D., Oh W.K. Roles of matrix metalloproteinases and their natural inhibitors in prostate cancer progression. Cancers. 2014;6:1298–1327.
19-Liu, B., Gu, X., Huang, T., Luan, Y., & Ding, X. (2017). Identification of TMPRSS2-ERG mechanisms in prostate cancer invasiveness: Involvement of MMP-9 and plexin B1. Oncology Reports, 37, 201-208.
20-Dilly AK, Ekambaram P, Guo Y, Cai Y, Tucker SC, Fridman R, Kandouz M, Honn KV. Platelet-type 12-lipoxygenase induces MMP9 expression and cellular invasion via activation of PI3K/Akt/NF-κB. Int J Cancer. 2013 Oct 15;133(8):1784-91.
21-Labrie M, St-Pierre Y. Epigenetic regulation of mmp-9 gene expression. Cell Mol Life Sci. 2013 Sep;70(17):3109-24.
22-Wilson SR, Gallagher S, Warpeha K, Hawthorne SJ. Amplification of MMP-2 and MMP-9 production by prostate cancer cell lines via activation of protease-activated receptors. Prostate. 2004 Jul 1;60(2):168-74.
23- Veras ASC, Correia RR, Batista VRG, Tavares MEA, Rubira RJG, Fiais GA, Giometti IC, Chaves-Neto AH, Teixeira GR. Aerobic physical exercise modifies the prostate tumoral environment. Life Sci. 2023 Nov 1;332:122097.
24-Giganti MG, Tresoldi I, Sorge R, Melchiorri G, Triossi T, Masuelli L, Lido P, Albonici L, Foti C, Modesti A, Bei R. Physical exercise modulates the level of serum MMP-2 and MMP-9 in patients with breast cancer. Oncol Lett. 2016 Sep;12(3):2119-2126.
25-Zheng A, Zhang L, Yang J, Yin X, Zhang T, Wu X and Ma X (2022) Physical activity prevents tumor metastasis through modulation of immune function. Front. Pharmacol. 13:1034129.
