Abstract
Background and Objective:
Colon cancer is one of the most prevalent malignancies of the gastrointestinal tract, and its progression is closely associated with dysregulation of apoptosis and activation of the hypoxia-dependent angiogenesis pathway. An imbalance in the Bax/Bcl-2 ratio and upregulation of the HIF-1α/VEGF-A axis are considered key molecular mechanisms underlying tumor cell survival. Although exercise is recognized as a safe non-pharmacological intervention, its effects on these molecular pathways in colon tumor tissue remain insufficiently clarified. Therefore, the present study aimed to investigate the effects of aerobic exercise on Bax/Bcl-2 balance and the HIF-1α/VEGF-A pathway in a rat model of DMH-induced colon cancer.
Methods:
This controlled experimental study was conducted on 40 male rats , randomly assigned to four groups: healthy control, sham, sedentary cancer, and cancer with aerobic exercise. Colon cancer was induced by dimethylhydrazine (DMH) injection, and the aerobic training protocol was implemented for 14 weeks. Gene expression levels of Bax, Bcl-2, HIF-1α, and VEGF-A in colon tumor tissue were quantified using RT-qPCR. Statistical analyses included the Shapiro–Wilk test, Levene’s test, one-way ANOVA, and Tukey’s post hoc test.
Results:
Colon cancer induction significantly increased tumor burden and significantly decreased Bax expression, while significantly increasing Bcl-2, HIF-1α, and VEGF-A expression in tumor tissue (all P < 0.001). In contrast, aerobic exercise significantly reduced tumor burden, significantly increased Bax expression, and significantly decreased Bcl-2, HIF-1α, and VEGF-A expression compared with the sedentary cancer group (all P < 0.01).
Conclusion:
Aerobic exercise in DMH-induced colon cancer–bearing rats was associated with increased Bax expression and reduced Bcl-2 expression (favoring apoptotic signaling), as well as decreased HIF-1α and VEGF-A expression (indicating modulation of the hypoxia-dependent angiogenesis pathway), accompanied by a reduction in tumor burden. These findings suggest that aerobic exercise may serve as a complementary non-pharmacological strategy to attenuate colon tumor progression.