The effects of eudurance exercise on expressionof myokines and tumor tissue in colon cancer-induced mice

Abstract

A few studies have demonstrated that exercise induces the release of cytokines from contracting muscles. These muscle-derived cytokines are collectively named myokines. Skeletal muscle is the largest organ in the human body, as an endocrine organ, muscle tissue has had a central role in orchestrating metabolism of other organs. The researchers have found a link between muscle contraction and these myokines in the form of an exercise factor. Recently accumulating evidence indicated that myokines may also play a role in cancer protection. It was shown that the contracting muscle by an acute exercise release humoral factors such as OSM, IL-10, SPARC that can inhibit cancer cell proliferation and induce cancer cell apoptosis. Base on the prevailing literature, the purpose of the present study was to investigate the impact of long-term exercise on expression of cytokines in muscle, blood and tumor tissue, thus to examine whether exercise mediates independent protective effect against cancer through the release of anti-proliferative proteins from contracting muscles according to exercise intensity. First, to identify the therapeutic effect of exercise, all mice at 6-wk old were injected AOM and were treated 3 cycles of DSS solution in drinking water to induce colon cancer. Then at 17-wk of old, mice of exercise groups performed treadmill exercise at different intensity (Low, Moderate, High) for 30 minutes, 5 days per week, during 12 weeks. Twenty-four hours after the last training session, all tissues were removed and blood samples were obtained. To analysis the effect of exercise, OSM and SPARC were evaluated in muscle, serum, and tumor tissue. Also related pro-apoptosis factor, caspase-3 in tumor tissue were analyzed. OSM was significantly overexpressed in exercise groups compare to controls

in gastrocnemius (p=.000), serum (p=.005), and tumor tissue (p=.000). Also, there was significant differences among exercise groups by exercise intensity on expression of OSM in colon-induced mice. The expression of OSM tends to increase in higher intensity in gastrocnemius (p=.000)

LIE (p= .014), MIE (p=.000), HIE (p=.000), in tumor tissue (p=.000)

LIE (p= .000), MIE (p=.000), HIE (p=.000), but only in serum of LIE (p=.000). The level of SPARC was significantly increased by exercise in muscle (p=.000), serum (p=.002), tumor tissue (p=.001) compare to controls. Also the expression of SPARC tends to increase in higher intensity in gastrocnemius (p=.001)

LIE (p= .035), MIE (p=.001), HIE (p=.007), in tumor tissue (p=.000)

MIE (p=.000), HIE (p=.000). The expression of caspase-3 increased significantly in MIE (p=.045). Secondly, to identify the preventive effect of exercise on colon cancer-induced mice, mice of exercise groups, at 6-wk of old, performed exercise at different intensity (Low, Moderate, High) for 30 minutes, 5 days per week, during 12 weeks. At 17-wk of old, all mice were injected AOM and were given 3 cycles of DSS solution in drinking water to induce colon cancer. Then they kept doing exercise for another 12 weeks. The level of OSM in muscle was significantly overexpressed in exercise groups compare to controls, however, not in blood and tumor tissue (p>.05). Also, there was significant differences among exercise groups by exercise intensity on expression of OSM in muscle. The expression of LIE (p=.001) and MIE (p=.000) were significantly increased than controls. However, the expression of OSM in blood was not increased by exercise intensity (p>.05). In the same time, the level of OSM in tumor tissue tends to increase by exercise intensity, but there was no statistical difference (p>.05). The level of SPARC was significantly increased by exercise in blood (p=.002), tumor tissue (p=.001) compare with controls, however, there was no significant difference in muscle (p>.05). However, the expression of SPARC in MIE was significantly higher than CON in gastrocnemius (p=.010). Also the expression of SPARC in tumor tissue tends to increase significantly by exercise intensity

MIE (p=.001), HIE (p=.000). Even though the expression of cleaved caspase-3 in tumor tissue tends to increase by exercise intensity, there was no statistical difference (p>.05). In conclusion, this study showed that exercise induced the expression of OSM and SPARC in several tissues by exercise stimulus, which is associated with inducing apoptosis in tumor cells. And the magnitude of OSM and SPARC induction in muscle and tumor tissue was relatively higher in moderate and high intensity exercise groups than low intensity exercise group. Moreover, moderate and high intensity exercise enhanced anti-apoptotic pathway in skeletal muscle, and increased gastrocnemius muscle weight. In addition, it is observed that the number of polyp generation in moderate and high intensity exercise group was significantly decreased than controls. Thus, the results of this study possibly suggest that moderate and high intensity exercise have more protective effect for colon cancer induced mice.