Vesnu Publications (Farzanegan Radandish) Journal of Exercise & Organ Cross Talk 2783-2074 6 2 2026 06 30 Differential hepatic gene regulation in melanoma: Combined exercise and anti-inflammatory supplementation selectively lowers CXCL2 but not bFGF2 82 89 241592 10.22122/jeoct.2026.574951.1192 EN Mahnaz Zarabadipour Department of physical education and sport sciences, SR.C., Islamic Azad university, Tehran, Iran. 0000-0002-6786-1425 Hossein Abednatanzi Department of physical Education and Sport Science, Science and research branch, Islamic Azad University, Tehran, Iran. 0000-0001-6638-1131 Mandana Gholami Department of physical education and sport sciences, SR.C., Islamic Azad university, Tehran, Iran. 0000-0001-8960-4123 Journal Article 2025 12 09 Hepatic gene expression of inflammatory and growth factors such as IL-8 and bFGF2 may be modulated in melanoma metastasis. Non-pharmacological interventions like exercise and anti-inflammatory supplements represent potential complementary strategies for modification. This study aimed to investigate the effects of aerobic exercise, pineapple extract supplementation, and their combination on the hepatic expression of CXCL2/IL-8 HOMOLOG and bFGF2 genes in a murine melanoma model. Melanoma-bearing mice were allocated into four groups (n=5 per group): Control, Aerobic Exercise, Pineapple Extract Supplement, and Aerobic Exercise+Pineapple Extract. After the intervention period, liver tissue was analyzed for CXCL2/IL-8 HOMOLOG and bFGF2 gene expression via one-way ANOVA and Tukey HSD test. Pearson correlation assessed the relationship between the two genes. A significant difference was observed in CXCL2/IL-8 HOMOLOG gene expression between groups (F=4.211, p=0.0239). Post hoc analysis revealed that only the combined Aerobic Exercise + Pineapple Extract group showed a significant decrease in hepatic CXCL2/IL-8 HOMOLOG compared to the Cancer Control group (p=0.0251). In contrast, no significant difference was found in bFGF2 gene expression across groups (F=1.425, p=0.2745). Correlation analysis indicated a significant negative relationship between CXCL2/IL-8 HOMOLOG and bFGF2 exclusively in the Cancer Control group (r=-0.948, p=0.013). The combination of aerobic exercise and pineapple extract supplementation significantly reduces hepatic CXCL2/IL-8 HOMOLOG expression in melanoma-bearing mice, suggesting a potential synergistic effect in modulating the hepatic inflammatory microenvironment. The distinct lack of effect on bFGF2 and the specific negative correlation in controls highlight pathway-selective responses. https://www.jeoct.com/article_241592_6caae5c19928cbdb53b9ca7aad7ac891.pdf