APC10.1 cells as a model for assessing the efficacy of potential chemopreventive agents in the Apc Min mouse model in vivo

Abstract

Apc Min mice are widely used for mechanism and efficacy studies associated with the development of chemopreventive agents. APC10.1 cells have been derived from Apc Min mouse adenomas and retain the heterozygous Apc genotype. We tested the hypothesis that this cell type may provide an in vitro model to predict chemopreventive activity of agents in the Apc Min mouse in vivo. The growth inhibitory properties of 14 putative colorectal cancer chemopreventive agents, tricin, apigenin, 3′,4′,5′,5,7-pentamethoxyflavone, resveratrol, curcumin, 3,4-methylenedioxy-3′,4′,5′-trimethoxychalcone (DMU135), 3,4,5,4′-tetramethoxystilbene (DMU212), celecoxib, aspirin, piroxicam, all- trans-retinoic acid, difluoromethylornithine (DFMO), quercetin and cyanidin-3-glucoside, were studied in this cell line, and the IC 50 values were calculated. The IC 50 values were plotted against previously published data of reduction of adenoma numbers caused by these agents in Apc Min mice. The correlation co-efficient was 0.678 ( p < 0.01), suggesting that there was a tentative correlation between the ability to inhibit the growth of APC10.1 cells and the ability to delay adenoma development in vivo. If this relationship is supported by using further agents, APC10.1 cells may serve in the future as an initial screen to prioritise compounds for assessing chemopreventive efficacy in Apc Min mice in vivo. Such a screen could reduce the number of animals required to find active agents, help reduce costs and increase throughput.