Reference SummaryRitland SR, Carcinogenesis 1999 Jan;20(1):51-8

Title

Chemoprevention of intestinal adenomas in the ApcMin mouse by piroxicam: kinetics, strain effects and resistance to chemosuppression.

Authors

Ritland SR; Gendler SJ

Journal

Carcinogenesis

Volume

Issue

Year

1999

Pages

51-8

Abstract

Previous cancer chemoprevention studies have demonstrated that NSAIDs can be effective in suppressing the development of intestinal tumors. To further explore this issue, we performed cross-over chemoprevention studies using the drug piroxicam in the Apc(Min) mouse to evaluate the kinetics of NSAID-mediated tumor regression, the effects of genetic background and the incidence of resistance to chemoprevention, Starting at the time of weaning, C57Bl/6J-Apc(Min) mice were fed either the control diet (AIN-93G) or AIN-93G plus 200 p.p.m. Piroxicam, Tumor multiplicity was significantly reduced in Apc(Min) mice that were fed 200 p.p.m. Piroxicam until 100 or 200 days of age (94.4 and 95.7% reduction in tumor number, respectively; P < 0.001 versus AIN-93G controls). When the administration of piroxicam was delayed until 100 days of age and the mice were killed at 200 days of age, tumor multiplicity was reduced by 96.2% (P < 0.001 versus controls), Alternatively, when the administration of piroxicam was suspended at 100 days of age and the mice were killed at 200 days of age, tumor multiplicity was reduced by 68.0% (P < 0.001 versus controls). Short-term drug treatment periods for Apc(Min) animals with established tumors revealed that the kinetics of piroxicam- induced tumor regression were rapid: >90% reduction in tumor multiplicity was observed after 1 week of treatment with 200 p.p.m. Piroxicam. The distribution of residual tumors in piroxicam-treated mice suggests that tumors of the duodenum and colon were relatively resistant to chemosuppression, Treatment of interspecific hybrid Apc(Min) mice with 200 p.p.m. Piroxicam revealed that there was a strain-related effect on chemosuppression, suggesting the existence of genetic elements which modulate NSAID chemosensitivity, Finally, whole-genome allelic loss studies showed that there were few unique chromosomal deletions in the NSAID-resistant tumors from F1 mice, implying that loss-of-function mutations secondary to Ape inactivation are not likely to account for the observed difference in chemoresistance.

Links

J:52249 – MGI References
9934849 – National Library of Medicine/PubMed

Strain Notes

Strain	Note
129X1B6F1-Apc^Min/+	C57BL/6J-Apc^Min/J males purchased from The Jackson Laboratory were mated with 129X1/SvJ females.
C57BL/6	C57BL/6J-Apc^Min/+ males purchased from The Jackson Laboratory were mated with C57BL/6 females.
C57BL/6-Apc^Min/+	C57BL/6J-Apc^Min/+ males purchased from The Jackson Laboratory were mated with C57BL/6 females.
FVBB6F1-Apc^Min/+	C57BL/6J-Apc^Min/+ males purchased from The Jackson Laboratory were mated with FVB females.

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency
C57BL/6-Apc^Min/+	Intestine - Large Intestine - Colon hyperplasia	piroxicam	Intestine - Large Intestine - Colon	observed
C57BL/6	Intestine - Large Intestine - Colon hyperplasia	piroxicam	Intestine - Large Intestine - Colon	observed
C57BL/6-Apc^Min/+	Intestine - Large Intestine - Colon tumor	piroxicam	Intestine - Large Intestine - Colon	observed
C57BL/6-Apc^Min/+	Intestine - Large Intestine - Colon tumor		Intestine - Large Intestine - Colon	observed
C57BL/6-Apc^Min/+	Intestine - Small Intestine - Duodenum tumor	piroxicam	Intestine - Small Intestine - Duodenum	observed
C57BL/6-Apc^Min/+	Intestine - Small Intestine - Duodenum tumor		Intestine - Small Intestine - Duodenum	observed
C57BL/6-Apc^Min/+	Intestine - Small Intestine - Ileum tumor		Intestine - Small Intestine - Ileum	observed
C57BL/6-Apc^Min/+	Intestine - Small Intestine - Jejunum tumor		Intestine - Small Intestine - Jejunum	observed
C57BL/6-Apc^Min/+	Intestine tumor		Intestine	observed
C57BL/6-Apc^Min/+	Intestine tumor	piroxicam	Intestine	observed
129X1B6F1-Apc^Min/+	Intestine tumor	piroxicam	Intestine	observed
129X1B6F1-Apc^Min/+	Intestine tumor		Intestine	observed
FVBB6F1-Apc^Min/+	Intestine tumor	piroxicam	Intestine	observed
FVBB6F1-Apc^Min/+	Intestine tumor	sulindac	Intestine	observed
FVBB6F1-Apc^Min/+	Intestine tumor		Intestine	observed