Abstract
PURPOSE: To determine if there are protective effects of habitual physical activity on chemotherapy-induced vascular toxicity.
METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured with 5% serum from healthy trained (n = 3) and untrained (n = 3) females. After 24 hours of serum preconditioning, HUVECs were exposed to physiological concentrations of 5-fluorouracil (5-FU), epirubicin, cyclophosphamide, and docetaxel (FEC-T). At 12 hours, the effects of exercise and chemotherapy on HUVEC viability and apoptosis were measured using intracellular flow cytometry. To assess endothelial repair, the preconditioned endothelial monolayer was scraped and exposed to FEC-T drugs. Wounds were imaged at 0, 3, 4, 6, 12, 24, and 48 hours to determine rate of gap closure.
RESULTS: FEC-T chemotherapy drugs decreased viability of HUVECs by 67 ± 6%, increased caspase-3 activity by 78 ± 4% and annexin-V expression by 88 ± 3% (all p < 0.05), compared to no drug control. Preconditioning HUVECs with serum from exercise trained females prior to chemotherapy exposure resulted in improved viability of HUVECs, and a reduction in caspase-3 and annexin-V expression compared to preconditioning with serum from untrained females (5-FU: viable HUVECs for trained: 73 ± 7% vs untrained: 54 ± 3%, p = 0.03; caspase-3 expression for trained: 27 ± 6% vs untrained: 60 ± 9%, p = 0.04; epirubicin: caspase-3 expression for trained: 34 ± 5% vs untrained 51 ± 1%, p = 0.04; annexin V expression for trained: 13 ± 1% vs untrained: 18 ± 1%, p = 0.03). FEC-T also resulted in impaired HUVEC wound healing by 100 ± 1% (p = 0.01). Preconditioning HUVECs with serum from trained individuals attenuated this impairment favourably over serum from untrained individuals (untrained Vmigration impairment: 10 ± 4% vs trained Vmigration impairment: 4 ± 1%, p = 0.02).
CONCLUSION: Our results confirm that FEC-T drugs commonly used in breast cancer treatment cause apoptosis the disruption of endothelial cell repair. Chemotherapy-induced endothelial cell apoptosis and impaired wound healing may be attenuated in exercise trained individuals.
METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured with 5% serum from healthy trained (n = 3) and untrained (n = 3) females. After 24 hours of serum preconditioning, HUVECs were exposed to physiological concentrations of 5-fluorouracil (5-FU), epirubicin, cyclophosphamide, and docetaxel (FEC-T). At 12 hours, the effects of exercise and chemotherapy on HUVEC viability and apoptosis were measured using intracellular flow cytometry. To assess endothelial repair, the preconditioned endothelial monolayer was scraped and exposed to FEC-T drugs. Wounds were imaged at 0, 3, 4, 6, 12, 24, and 48 hours to determine rate of gap closure.
RESULTS: FEC-T chemotherapy drugs decreased viability of HUVECs by 67 ± 6%, increased caspase-3 activity by 78 ± 4% and annexin-V expression by 88 ± 3% (all p < 0.05), compared to no drug control. Preconditioning HUVECs with serum from exercise trained females prior to chemotherapy exposure resulted in improved viability of HUVECs, and a reduction in caspase-3 and annexin-V expression compared to preconditioning with serum from untrained females (5-FU: viable HUVECs for trained: 73 ± 7% vs untrained: 54 ± 3%, p = 0.03; caspase-3 expression for trained: 27 ± 6% vs untrained: 60 ± 9%, p = 0.04; epirubicin: caspase-3 expression for trained: 34 ± 5% vs untrained 51 ± 1%, p = 0.04; annexin V expression for trained: 13 ± 1% vs untrained: 18 ± 1%, p = 0.03). FEC-T also resulted in impaired HUVEC wound healing by 100 ± 1% (p = 0.01). Preconditioning HUVECs with serum from trained individuals attenuated this impairment favourably over serum from untrained individuals (untrained Vmigration impairment: 10 ± 4% vs trained Vmigration impairment: 4 ± 1%, p = 0.02).
CONCLUSION: Our results confirm that FEC-T drugs commonly used in breast cancer treatment cause apoptosis the disruption of endothelial cell repair. Chemotherapy-induced endothelial cell apoptosis and impaired wound healing may be attenuated in exercise trained individuals.
| Original language | English |
|---|---|
| Pages (from-to) | 444-445 |
| Number of pages | 2 |
| Journal | Medicine & Science in Sports & Exercise |
| Volume | 53 |
| Issue number | 8S |
| DOIs | |
| Publication status | Published - 31 Aug 2021 |
| Externally published | Yes |
