Abstract B49: Effects of exercise on ovarian cancer initiation and progression

Abstract

Abstract Epidemiology studies support a strong association between physical activity and lower risk of cancer. Exercise is a promising nonpharmacologic strategy in preventing cancer and mitigating adverse effects of cancer and anticancer therapies. However, we have not been able to optimize the efficacy of exercise training as an anticancer intervention due to the lack of knowledge regarding the biologic mechanisms of action, the effective doses, and the biomarkers for predicting and monitoring responses of exercise-based intervention. Our objective is to utilize mouse models to determine the effects and underlying mechanisms of exercise on ovarian cancer initiation and progression. C57BL/6 mice ran on a treadmill for 45min daily to mimic human exercise activity. The control groups were placed on treadmill for 45min daily. After a month of this exercise regiment, both groups were injected with cancer cells derived from ovarian tumors of Dicer-/-; Pten-/-; Tp53R172H mice. Tumor progression was monitored through IVIS imaging system. Blood and peritoneal fluid samples were tested for cytokine levels. Tissue samples were collected and gene expression levels were quantified via qPCR. Peritoneal macrophages were isolated after acute exercise and were used in flow cytometry analysis or cocultured with cancer cells. Our model resembled the biologic changes of exercise in human. Eight-week treadmill-running exercise suppressed early tumor formation and tumor spreading. Exercise altered visceral fat tissue gene expression profile, which may inhibit cancer-induced cachexia and metabolic imbalance. In addition, one-hour exercise induced the acute proinflammatory activation of peritoneal macrophages. Coculture of peritoneal macrophages and PBMC (peripheral blood mononuclear cells) or NK (natural killer) cells from the exercise group and cancer cells reduced survival of cancer cells. Chronic and acute exercise can both suppress ovarian cancer tumorigenesis in mouse models. The underlying mechanisms involve enhancing anticancer immune system responses and adjusting metabolic balance. More research is needed to determine the specific mechanisms by which chronic and acute exercise affects ovarian cancer. Citation Format: Fangfang Bi, Madeline Morrisson, Sarah Cady, Alexandra Cerchia, Kevin Yang, Ivy Ling, Yang Yang-Hartwich. Effects of exercise on ovarian cancer initiation and progression [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B49.