The effect of exogenous prostaglandin administration on tumor size and yield in Min/+ mice.
This study set out to examine the effect of exogenous prostaglandin (PG) administration on tumor development in Min/+ mice. Mice were treated with the stable prostaglandin E2 analogue 16,16-dimethyl-PGE2 from 6-18 weeks of age. Mice were sacrificed, and tumor burden was assessed using morphometric techniques. Parameters measured were median tumor size, mean tumor size, the proportion of the area of the gastrointestinal mucosa covered with tumor, and the number of tumors per 1000 mm2 of gastrointestinal mucosa. In addition, proliferative and apoptotic indices were determined. These measurements were carried out for all regions of the small intestine (i.e., duodenum, jejunum, upper ileum, and lower ileum) and the large intestine (i.e., cecum and mid-colon/rectum). 16,16-Dimethyl-PGE2-treated animals showed a significant decrease in tumor burden (by approximately 50-70%), in comparison with those animals that were treated with vehicle alone (0.001% ethanol in 0.9% sterile saline), in all regions of the intestine (at P = 0.008 or better). This effect was contributed to by a reduction in the number of tumors (by approximately 20-50%) and a reduction in tumor size (by approximately 10-70%). An increase in tumor cell turnover was associated with this decrease in tumor burden, as determined by the changes in the levels of thymidine incorporation (significant at P = 0.003), apoptosis, and mitosis (nonsignificant).
Wilson
J W
JW
Section of Cell and Tumour Biology, Paterson Institute for Cancer Research, Manchester, United Kingdom. jwilson@picr.man.ac.uk
Potten
C S
CS
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004379:Duodenal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D007078:Ileal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D015064:16,16-Dimethylprostaglandin E2; D013936:Thymidine