Exercise Training and Nanocurcumin Induce Down-regulation of EGFR/MAPK/STAT5/FN14 Pathway Genes in Tumor Tissue of Glioblastoma Multiform Model Rats

 Since EGFR inhibitors show a limited therapeutic effect on Glioblastoma multiforme patients, the EGFR/MAPK/STAT5/FN14 signaling pathway becomes vulnerable to the invasive GBM cell population and may be a suitable target for the treatment of GBM. Nanocurcumin consumption and exercise training are probably effective interventions in this signaling pathway.

 This study aimed to investigate the simultaneous effects of exercises training and Nanocurcumin consumption on the EGFR/MAPK/STAT5/FN14/FN14 pathway in the tumor tissue of GBM model rats.

 In this study, 40 male Wistar rats were randomly assigned to five groups: 1- control (CON), 2- glioblastoma multiform (GBM), 3- glioblastoma multiform+concurrent training (GBM+CT), 4- glioblastoma multiform+nanocurcumin (GBM+NC), and 5- glioblastoma multiform+nanocurcumin+concurrent training (GBM+NC+CT) groups. The target groups performed aerobic training (20 - 35 minutes at 18 m/min) along with resistance training (climbing the ladder in three sets repeated four times) and received Nanocurcumin at the rate of 100 mg.kg-1.day-1 for four weeks. Gene expression was measured by real-time PCR. Two-way analysis of variance was used for analyzing data.

 According to our study results, concurrent training significantly reduced the expressions of EGFR, MAPK, STAT5, and Fn14, mRNA compared with GBM group (P < 0.05). Furthermore, nanocurcumin significantly reduced the expressions of EGFR, MAPK, as well as Fn14, mRNA compared with GBM group (P < 0.05). Nanocurcumin+Concurrent training decreased the expressions of EGFR, MAPK, STAT5 as well as Fn14, and mRNA compared with the GBM group (P < 0.05). A significant reduction was recorded for all mRNA expression levels in the GBM+NC+CT group compared with those in the GBM+NC group (P < 0.05).

 In sum, combined exercises and nano curcumin consumption may have been adopted as a non-pharmacological strategy to modulate the expression of EGFR/MAPK/STAT5/FN14 genes in tumor tissue of glioblastoma multiform.