New Study: How Exercise Boosted Chemotherapy in Mice

A 2021 study demonstrated how exercise impacts a highly-prescribed chemotherapeutic agent, doxorubicin, in murine models of breast cancer.

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Most people are aware by now that exercise has positive effects in “healthy” individuals and in patients with cancer. In cancer patients, exercise has been shown to reduce adverse events, improve quality-of-life and respiratory fitness, and even to decrease the risk of breast cancer recurrence. These results, and many others, have prompted major national and international cancer organizations to promote exercise recommendations for the general public.

“There also is a growing body of evidence that exercise may directly alter the tumor microenvironment to influence tumor growth, metastasis, and response to anticancer therapies.”

However, scientists and researchers have only scratched the surface of understanding the extent of the benefits that are capable of being harnessed by exercise. While research shows that exercise may impact tumors, the exercise prescription needed to induce these beneficial tumor-related outcomes is still unclear. In an effort to better harness the benefits of exercise, researchers from the University of Florida conducted a study on the effects of wheel running in breast cancer mouse models and chemotherapy. Their paper was published as the cover of Oncotarget’s Volume 12, Issue 18, and entitled, “Normal tissue and tumor microenvironment adaptations to aerobic exercise enhance doxorubicin anti-tumor efficacy and ameliorate its cardiotoxicity in retired breeder mice.”

“The goal of this study was to characterize the exercise prescription by evaluating the aerobic adaptations in both the normal tissue and the tumor microenvironment. Moreover, doxorubicin was used to assess the adjuvant effects of aerobic exercise on chemotherapy efficacy and toxicity.”

The Study

In this study, the researchers employed retired female breeder BALB/c mice. The control arm was mice without breast cancer, divided into non-exercising and exercising groups. Study arm mice were intraductally inoculated with breast cancer cells, and then randomized into non-exercising and exercising groups. The exercising mice had 24/7 access to running wheels. The researchers found that voluntary use of the exercise wheel increased steadily throughout the first week, and then plateaued over the course of the rest of the 30-day study.

To further observe the effects of voluntary exercise in combination with a highly-prescribed chemotherapeutic drug, doxorubicin hydrochloride was delivered to the study mice in three doses, over a period of seven days. Control mice received an equivalent volume of phosphate buffered saline. Researchers measured the activity of a marker for mitochondrial density and oxidative capacity (citrate synthase enzyme), as well as circulating levels of a marker for cardiac damage (cardiac troponin I). The team evaluated intratumoral hypoxia using immunoblotting and performed global metabolomics profiling to investigate the impact of exercise on tumor metabolism.

“In the present study, aerobic exercise improved doxorubicin’s anti-tumor efficacy, and also reduced its cardiotoxicity, implying that the inclusion of exercise in a therapeutic regimen led to a therapeutic gain.”

Conclusion

Daily, voluntary exercise in these mice with breast cancer was found to enhance the anti-tumor effects of doxorubicin, while also blunting this drug’s cardiotoxic effects. The researchers note that future studies are needed and were forthcoming about a limitation in this study. While non-tumor bearing mice were included in the data colected in the cardiotoxicity leg of the experiment, the authors maintain that the improved cardiotoxicity observed after aerobic exercise in tumor bearing mice was still very encouraging.

“Future studies will establish if these effects hold true in clinical oncology populations in addition to providing the well-known physical and psychological benefits of exercise [49].”

Click here to read the full research paper, published by Oncotarget.

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