Preclinical Study Suggests Benefits of Increased Tumor Perfusion and Reduced Tumor Hypoxia With Exercise in Prostate Cancer


Key Points

  • In an orthotopic model, exercise induces increased prostate tumor blood flow.
  • Tumor hypoxia is reduced, reflecting reduced vasoconstriction.

In a study reported in the Journal of the National Cancer Institute, McCullough et al used an orthotopic rat model of prostate cancer to assess the effects of exercise on tumor hemodynamics and tissue hypoxia. Their findings of enhanced tumor perfusion and diminished tumor hypoxia suggest that exercise may improve drug delivery to the tumor and, by reducing hypoxia, help convert disease to a less aggressive form.

Study Details

The study involved measurement of prostate tumor blood flow, vascular resistance, patent vessel number, and hypoxia in vivo in conscious orthotopic tumor-bearing (Dunning R-3327 MatLyLu tumor cells) and control rats at rest and during treadmill exercise. Vasoconstrictor responsiveness of resistance arterioles was measured in vitro.

Increased Perfusion, Decreased Hypoxia

Exercise resulted in an approximately 200% increase in prostate tumor blood flow (P ≤ .001), resulting in an increase in oxygen delivery from 3.0 mL O2/min/100 g at rest to 9.3 mL O2/min/100 g. Vascular resistance in the prostate tumor was significantly greater at rest when compared with prostate tissue of control rats and the host prostate of tumor-bearing rats. During the rest-to-exercise transition, prostate tumor vascular resistance decreased by approximately 65%, whereas resistance increased slightly in the host prostate and prostates in the control group (P ≤ .001).

The number of patent vessels significantly increased (mean, 14.3 vs 12.7, P = .02) and hypoxia significantly decreased (hypoxic fraction = 15.4% vs 35.5%, P < .001) during exercise vs rest. In tumor arterioles, the maximal constriction induced by norepinephrine was decreased by approximately 95% vs control prostate vessels (3.4% vs 87.5%, P ≤ .001).

The investigators concluded, “During exercise there is enhanced tumor perfusion and diminished tumor hypoxia due, in part, to a diminished vasoconstriction. The clinical relevance of these findings are that exercise may enhance the delivery of tumor-targeting drugs as well as attenuate the hypoxic microenvironment within a tumor and lead to a less aggressive phenotype."

Bradley J. Behnke, PhD, of University of Florida, Gainesville, is the corresponding author for the Journal of the National Cancer Institute article.

The study was supported by the National Institutes of Health and the Florida Biomedical Research Program.

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