Exercise protection of vascular endothelial cells against breast cancer chemotherapy toxicity: Evidence from in vitro serological studies

Mclaughlin, Marie

Abstract

5-fluorouracil, epirubicin, cyclophosphamide, and docetaxel is an effective chemotherapy regimen for early-stage breast cancer (BC). However, these drugs associate with a 5% incidence of heart failure (HF). To attenuate the cardiovascular toxicity of chemotherapy, exercise has been proposed as a potential preventative measure. There is now emerging evidence for protective effects of exercise on the heart but there is a lack of evidence for vascular effects, despite vascular endothelial dysfunction being an initiating step in cardiovascular disease (CVD) development.

This study aimed to determine if there are protective effects of habitual physical activity, a single acute exercise session, and an exercise training intervention on chemotherapyinduced vascular endothelial cell toxicity. It was hypothesised that serological factors in active women can alleviate vascular toxicity from chemotherapy; and an acute exercise session and an exercise training intervention can alleviate toxicity in previously sedentary women.

To investigate protective effects of exercise, a novel ex vivo method was used. Endothelial cell cultures were preconditioned with serum from active and sedentary woman; woman pre- and post-acute exercise bout; and woman pre- and post-exercise intervention. After 24-hours of serum preconditioning, endothelial cells were exposed to physiological concentrations of 5-fluorouracil, epirubicin, cyclophosphamide, and docetaxel. Cell viability and function, and wound repair were assessed using flow cytometry and scratch assays (to simulate a wound), respectively.

Overall, results confirm that FEC-T chemotherapy drugs, commonly used in early-stage BC treatment, elicit significant damage and dysfunction of endothelial cells. Exercise serum preconditioning from active women, serum collected after an acute exercise session, and serum collected after an exercise training intervention, elicited some protection of endothelial cells against the usual toxicity of 5-fluorouracil, epirubicin, cyclophosphamide, and docetaxel, when compared to control serum preconditioning from inactive women, serum collected prior to an acute exercise session, and serum collected prior to an exercise training intervention, respectively.

Citation

Mclaughlin, M. Exercise protection of vascular endothelial cells against breast cancer chemotherapy toxicity: Evidence from in vitro serological studies. (Thesis). Edinburgh Napier University. Retrieved from http://researchrepository.napier.ac.uk/Output/2951034

• Thesis Type: Thesis
• Deposit Date: Nov 8, 2022
• Publicly Available Date: Nov 8, 2022
• DOI: https://doi.org/10.17869/ENU.2022.2951034
• Public URL: http://researchrepository.napier.ac.uk/Output/2951034
• Award Date: Jul 6, 2022