Voluntary exercise inhibits intestinal tumorigenesis in Apc(Min/+) mice and azoxymethane/dextran sulfate sodium-treated mice.
BACKGROUND
Epidemiological studies suggest that physical activity reduces the risk of colon cancer in humans. Results from animal studies, however, are inconclusive. The present study investigated the effects of voluntary exercise on intestinal tumor formation in two different animal models, Apc(Min/+) mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice.


METHODS
In Experiments 1 and 2, five-week old female Apc(Min/+) mice were either housed in regular cages or cages equipped with a running wheel for 6 weeks (for mice maintained on the AIN93G diet; Experiment 1) or 9 weeks (for mice on a high-fat diet; Experiment 2). In Experiment 3, male CF-1 mice at 6 weeks of age were given a dose of AOM (10 mg/kg body weight, i.p.) and, 12 days later, 1.5% DSS in drinking fluid for 1 week. The mice were then maintained on a high-fat diet and housed in regular cages or cages equipped with a running wheel for 16 weeks.


RESULTS
In the Apc(Min/+) mice maintained on either the AIN93G or the high-fat diet, voluntary exercise decreased the number of small intestinal tumors. In the AOM/DSS-treated mice maintained on a high-fat diet, voluntary exercise also decreased the number of colon tumors. In Apc(Min/+) mice, voluntary exercise decreased the ratio of serum insulin like growth factor (IGF)-1 to IGF binding protein (BP)-3 levels. It also decreased prostaglandin E2 and nuclear beta-catenin levels, but increased E-cadherin levels in the tumors.


CONCLUSIONS
These results indicate hat voluntary exercise inhibited intestinal tumorigenesis in Apc(Min/+) mice and AOM/DSS-treated mice, and the inhibitory effect is associated with decreased IGF-1/IGFBP-3 ratio, aberrant beta-catenin signaling, and arachidonic acid metabolism.
Ju
Jihyeung
J
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA. jujih@rci.rutgers.edu
Nolan
Bonnie
B
Cheh
Michelle
M
Bose
Mousumi
M
Lin
Yong
Y
Wagner
George C
GC
Yang
Chung S
CS
D000818:Animals; D001397:Azoxymethane; D014408:Biomarkers, Tumor / Q000097:blood*; D015820:Cadherins / Q000378:metabolism; D002273:Carcinogens; D018389:Codon, Nonsense; D016264:Dextran Sulfate; D004041:Dietary Fats / Q000008:administration & dosage; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D017491:Genes, APC / Q000502:physiology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000097:blood* / Q000139:chemically induced / Q000517:prevention & control*; D007421:Intestine, Small; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
D014408:Biomarkers, Tumor; D015820:Cadherins; D002273:Carcinogens; D018389:Codon, Nonsense; D004041:Dietary Fats; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D051176:beta Catenin; D016264:Dextran Sulfate; D015232:Dinoprostone; D001397:Azoxymethane