The Role Of Aerobic Physical Training On Colon Tumor Metabolic Reprogramming

PURPOSE: Tumor cells are known for marked growth and proliferation, however adequate energy support is required to sustain the growth and proliferation of cancer cells. Therefore, tumors have a large change in energy metabolism, for example, the glycolysis pathway is overactivated. These phenomena are linked to changes in metabolic genes expression, such as microRNA-33a and its gene target SIRT6. On the other hand, aerobic physical training (APT) is known to increase cellular respiration in tissues such as cardiac and skeletal muscle, unlike cancer. APT, also contributes to decreased tumor progression. METHODS: We first evaluated if a longer training time prior colon cancer cell inoculation (CT26) contributes to lower tumor progression, we observed that the time of APT is not a major factor since all cancer trained mice have lower tumor progression compared to the sedentary cancer group (SC). Thus, we proceeded to evaluate two groups: 1) group with cancer and 8-weeks training prior to inoculum (TR8), 2) and SC and 3) Wild type (WT). RESULTS: TR8 group presented longer survival (p=0.007), cancer promoted decrease of fat mass (WT-7.3±0.7; SC-1.4±0.8; TR8-3.6±2.8; p=0.01) and increase of liver mass (WT-62±7.9; SC-91.7±11.9; TR8-81.5±11; p=0.01) in sedentary e trained group compared with WT. SIRT6 (SC-100±12.1; TR8-88.8±27.9) and the microRNA-33a (SC-100±42.9; TR8-78.2±30.6) expression in tumor tissue was not different between the groups. However, we observed differences in HIF1a expression (SC-100±21.4;TR8-74±13.4 - p=0.01), which was decreased due to APT, as well as the GLUT1 (SC-100±32.4; TR8-69.6±36.2; p=0.07), PDK (SC-100±20.9;TR8-76.8±22.6; p=0.05), LDHa (SC-100±26.2;TR8-65.4±35.7 p=0.03) expression also decreased due to APT. CONCLUSIONS: Our results show that APT decreases tumor progression and increases survival. Also, our results suggest that APT plays an important role in metabolic reprogramming. In conclusion, we showed that APT decreases the glycolytic pathway enzymes gene expression that is related to increased proliferation and malignancy of colon cancer.