Dipyridamole (DPM) is widely used to prevent
strokes and vascular
thrombosis. Combination
therapy of DPM and
antimetabolites has shown synergistic anticancer activity. This study investigated the chemopreventive effects of DPM in the mouse mammary tumor virus promoter-driven polyoma middle T
oncoprotein metastatic
breast cancer model. We also investigated the effects of DPM on gene and
miRNA expression. Chemopreventive activity was assessed by comparing the time to onset of palpable lesions, primary
tumor growth kinetics, and the number of lung
metastases in transgenic mice treated with DPM or vehicle. Gene expression and
miRNA expression profiles of mammary
tumor tissues were then analyzed using the Affymetrix GeneChip or
miRNA 2.0 arrays. Real-time quantitative PCR was used to confirm changes in gene expression. Treatment with DPM beginning at the age of 4 weeks delayed the onset of palpable lesions, delayed
tumor progression, and suppressed lung
metastasis. Microarray gene expression analysis identified 253 genes differentially expressed between DPM-treated and control mammary
tumors.
miRNA expression analysis revealed that 53
miRNAs were altered by DPM treatment. The results indicate that DPM has
chemoprevention activity against
breast cancer tumorigenesis and
metastasis in mice. The array analyses provide insights into potential mechanisms of DPM's chemopreventive effects, involving upregulation of several genes and
miRNAs known to suppress
cancer growth and/or
metastasis and downregulation of genes known to promote
cancer. Some of these genes have not been previously studied in
breast cancer and may serve as novel molecular targets for
breast cancer chemoprevention.