通过下调 Myc 和 E2F 靶基因并诱导自噬性凋亡，重新利用达比加群酯以改善前列腺癌的预防和治疗

Dabigatran etexilate (DAB), an FDA-approved oral anticoagulant drug, has been safely used in cancer patients. While it has been concurrently administered with anti-androgens like enzalutamide in some prostate cancer patients, the potential interactions between DAB and enzalutamide and their effects on prostate cancer cells remain unknown. In this study, we have shown that DAB selectively inhibited prostate cancer cell growth with minimal growth inhibitory effects on normal prostate epithelial cells. Dabigatran induced autophagic apoptosis as evidenced by LC3B/Caspase 3 cleavages and increased autophagic vesicles. Oral administration of DAB significantly inhibited in vivo tumor growth in a xenograft model of 22Rv1 cells and reduced AR and Ki67 expression levels in tumor tissues. A systematic transcriptome analysis of gene expression regulation in DAB treated 22Rv1 cells revealed that the DAB regulated genes were significantly enriched in c-Myc and E2F targets and apoptosis and G2M checkpoint related genes. In addition, DAB acted synergistically with enzalutamide to reduce cell viabilities of prostate cancer cell lines: 22Rv1 and MyC-CaP. Our results indicate that DAB deserves further investigation as a novel anti-cancer agent, for prostate cancer prevention and for treatment of prostate cancer in combination with the main clinically used drug enzalutamide.