Acute and lifelong exercise modulate the tumorigenic potential of human lung cancer cells and their susceptibility to cisplatin.

Abstract

The association between higher levels of physical activity and lower cancer risk and mortality is well established. However, a causal link is yet to be proven. Recent studies showed a decrease in the proliferation rates of cultured human cancer cells when the human serum used to stimulate them was conditioned by acute exercise. Here, we tested the hypothesis that serum mediates some of the putative benefits of exercise on cancer through alterations to the growth pattern and susceptibility to chemotherapy agents of cancer cells. To this end, human non-small cell lung cancer cells were exposed to serum, collected before or after an acute exercise intervention, from two cohorts that differed significantly in their levels of physical activity and, accordingly, cardiorespiratory fitness, but were otherwise identical (non-exercisers and master athletes). Serum levels of glucose, lipids, albumin, C-reactive protein and cytokines were determined, and the impact of the serum responses to acute and lifelong exercise on cancer cell growth pattern and susceptibility to cisplatin were analysed. We found that acute exercise decreased the proliferation rate of the cells, yet shortened the lag phase of the cells after detachment, whereas lifelong exercise had the opposite effects. Significantly, we showed, for the first time, that lifelong exercise increased susceptibility to a chemotherapy agent, which might contribute to the decreased cancer mortality rates found among those cancer patients who exercise regularly. Similar to the cellular effects, changes to serum cytokine levels (several of them linked to the senescence-associated secretory phenotype) depended on whether serum was conditioned by acute exercise or by lifelong exercise.