Table 4.
Effects of exercise on tumor progression and metastasis in mouse models.
| Tumor type (study) | Rodent model | Animal strain | Method of tumor initiation | Effect of exercise on primary tumor growth (% of control) | Description of primary tumor growth | Description of mechanistic findings
|
||
|---|---|---|---|---|---|---|---|---|
| Intratumoral | Systemic | |||||||
| Breast adenocarcinoma (Cohen et al., 1991) | Rat | F344 | Tail vein injection of 37.5 mg/kg NMUb | Inhibition (NE) | Exercise significantly delayed tumor appearance and increased tumor latency. Tumor incidence was significantly lower in exercised animals compared with controls. There was no significant difference in tumor burden or mean tumor volume | Not evaluated | Exercise did not significantly affect prolactin levels | |
| (Hoffman-Goetz et al., 1994a,b) | Mouse | BALB/c | Lateral tail vein injection of 1 × 104 MMT 66 cells | Not evaluated | This study evaluated pulmonary metastases from a tail vein injection of tumor cells. Exercise beginning after tumor injection did not significantly affect multiplicity of lung metastases | Not evaluated | Mice that began running on a voluntary wheel only after tumor injection had significantly higher LAK cell activity than those that had access to a voluntary running wheel before and after tumor injection | |
| (Jones et al., 2005) | Mouse | Athymic nu/nu | Subcutaneous injection of 5 × 106 MDA-MB-231 cells | No change (NE) | There was no significant difference in tumor growth delay | Not evaluated | Not evaluated | |
| (Saez Mdel et al., 2007) | Rat | Sprague– Dawley | Gastric intubation of DMBA.c 5 mg weekly for 4 w. | Augmentation (+200%) | The exercise group had a significantly higher tumor growth rate. There were no significant differences in survival time or tumor multiplicity | Not evaluated | Not evaluated | |
| (Jones et al., 2010a,b,c) | Mouse | Athymic | Orthotopic (dorsal mammary fat pad) injection of 1 × 106 MDA-MB-231 cells | No change (+21%) | There was no significant difference in survival time based on tumor growth to 1500 mm3 | The exercised group had significantly more perfused vessels. HIF-1 protein levels were significantly higher in the viable tumor the exercised group. There were no significant differences in the levels of CD31, VEGF, ATP, PGC-1α, or AMPK | Not evaluated | |
| Sarcoma (Hoffman et al., 1962) | Rat | Wistar | Subcutaneous injection of 2 cc of Walker 256 cell suspension (concentration not specified) | Inhibition (− 97%) | Tumor weight was significantly lower in the exercise group | Not evaluated | Not evaluated | |
| (Uhlenbruck and Order, 1991) | Mouse | BALB/c | Subcutaneous injection of 2.5 × 104 L−1 cells | Inconclusive (−44% to +86%) | The group that ran 200 m daily had significantly lower tumor weights, but the other running distances did not significantly affect tumor weight | Not evaluated | Not evaluated | |
| (Foley et al., 2004) | Rat | F344 | Subcutaneous injection of 1 × 107 C10 cells | No change (− 31%) | There was no significant difference in tumor weight as a result of exercise | Not evaluated | Exercise significantly increased insulin-stimulated glucose transport. No significant differences in blood glucose levels or lipid peroxidation in skeletal muscle based on exercise treatment | |
| Hepatoma (Baracos, 1989) | Rat | Sprague– Dawley | Subcutaneous injection of 20 μL Morris hepatoma 777 finely chopped tumors | Inhibition (− 25%) | Tumor weight was significantly lower in the exercise groups. No significant differences in tumor weight between groups exercised for different durations | Not evaluated | Not evaluated | |
| Pancreatic adenocarcinoma (Roebuck et al., 1990) | Rat | F344, Lewis | F344 rats received 3 doses of 30 mg/kg azaserine 4–5 d apart. Lewis rats received one dose of 30 mg/kg azaserinea | Inconclusive (−1% to −11%) | F344 rats that were exercised had significantly fewer foci and smaller volume percentage of foci, but there was no difference in focal diameter. No significant differences in Lewis rats | No significant difference in the amount of DNA synthesis based on treatment condition | Not evaluated | |
| Transformed salivary gland cells (Japel et al., 1992) | Mouse | NMRI | Subcutaneous injection of 1.5 × 106 S-180 cells | Not evaluated | Not evaluated | Not evaluated | Moderate intensity physical exercise begun after injection of tumor cells did not significantly change macrophage phagocytosis | |
| Transformed fibroblasts (MacNeil and Hoffman-Goetz, 1993) | Mouse | C3H/He | Lateral tail vein injection of 3 × 105 CIRAS1 cells | Not evaluated | This study evaluated pulmonary metastases from a tail vein injection of tumor cells. Exercise beginning after tumor injection did not alter lung tumor density relative to sedentary controls | Not evaluated | Not evaluated | |
| Neoplastic lymphoid cells (Zielinski et al., 2004) | Mouse | BALB/c | Subcutaneous injection of 2 × 107 EL-4 cells | Inconclusive (+5%) | Exercise significantly delayed tumor appearance. There was no significant difference in peak tumor volume. Non-syngeneic tumors were rejected by the immune system of exercised mice | No significant difference in the fluid content of tumors. Significant reduction in vessel density in exercised animals on days 6, 8, 10, and 14 compared to controls | Not evaluated | |
| Prostate adenocarcinoma (Zheng et al., 2011) | Mouse | SCID | Subcutaneous injection of 2.5 × 106 LNCaP cells. Tumors grew for 4–6 wk then animals were castrated to mimic androgen deprivation | Inhibition | Voluntary wheel running moderately inhibited androgen-independent tumor growth | Not evaluated | Not evaluated | |
a
Azaserine is a glutamine analog carcinogen used to induce pancreatic cancer in preclinical models.
b
N-Nitroso-N-methylurea (NMU) is an alkylating agent used to induce breast cancer.
c
7,12-Dimethylbenzanthracene (DMBA) is an aromatic hydrocarbon used to induce breast cancer.