Effect of High-intensity Interval Training Combined with Pomegranate Juice Supplementation on the Granulocyte Colony-Stimulating Factor Signaling Pathway in an Animal Model of Colorectal Cancer Induced by CT26 Cell Line

Background: Low-cost and non-toxic approaches for treating colorectal cancer (CRC) have garnered significant attention from researchers in recent years. Objectives: This study aimed to investigate the effect of high-intensity interval training (HIIT) combined with pomegranate juice (PJ) consumption on the granulocyte colony-stimulating factor (G-CSF) signaling pathway in an animal model of CRC induced by the CT26 cell line. Methods: In this experimental study, 24 male BALB/c mice (weight: 18 - 22 g, age: 8 - 10 weeks) with CRC induced by injection of 5 × 105 viable CT26 cells were randomly divided into four groups: (1) CRC, (2) PJ, (3) HIIT, and (4) HIIT + PJ. Additionally, 6 healthy control (HC) mice were included to assess CRC's effects on study variables. The HIIT protocol was conducted over eight weeks, with 5 - 16 sets of high-intensity sets, at 75 - 90% maximum speed on a 15-degree incline. Pomegranate juice supplementation constituted 5% of daily drinking water. Results: The levels of G-CSFR, Janus kinase 2 (JAK2), STAT3, mitogen-activated protein kinase (MAPK), and ERK were significantly elevated in the Ca group compared to the HC group (P = 0.001). Conversely, the PJ, HIIT, and HIIT+PJ groups exhibited significantly lower levels of G-CSFR, JAK2, STAT3, MAPK, and ERK compared to the Ca group (P = 0.001). Notably, the HIIT+PJ group showed significantly reduced levels of G-CSFR (P = 0.02) and JAK2 (P = 0.001) compared to the PJ group. JAK2 levels were also significantly lower in the HIIT group compared to the PJ group (P = 0.001). Furthermore, STAT3 levels were significantly lower in the PJ and HIIT+PJ groups compared to the HIIT group (P = 0.001), with the HIIT+PJ group also showing significantly lower levels than the HIIT group (P = 0.001). Finally, MAPK and ERK levels were significantly lower in the HIIT+PJ group compared to both the PJ (P = 0.005) and HIIT (P = 0.001) groups. Conclusions: While colon cancer induction increases G-CSFR, JAK2, STAT3, MAPK, and ERK gene expression in the intestinal tissue of laboratory mice, both HIIT and PJ, independently and synergistically, can reduce the expression of these genes through similar antioxidant and anti-inflammatory pathways in the intestinal tissue of mice with colon cancer.