Discovery of drugs and the underlying mechanisms for the treatment of Ac-KLF5-mediated prostate cancer bone metastasis

Prostate cancer is a common male malignancy, with high frequency of bone metastases that are associated with life-threatening mortality. Recently, given that acetylated-KLF5 plays a critical role in promoting prostate cancer bone metastasis (PCBM), actylated-KLF5 may be a potential therapeutic strategy. In this study, we identified nitazoxanide, an FDA-approved anthelmintic agent with remarkable inhibitory activity against acetylated-KLF5 induced bone metastasis. RNA sequencing was performed on PC3-KQ and PC3-KR cells in the presence or absence of NTZ (5 μM). We identified 268 differentially expressed genes, which are upregulated (127) or downregulated (114) in KQ cells compared to KR cells and can be reversed by NTZMechanistically, nitazoxanide downregulated MYBL2 and TIMM8A and upregulated CALB1, COL4A4, COL4A3, SPOCK2, and TMPRSS2, which was associated with a better overall survival. Prostate cancer mRNA profiles of DMSO-treated and NItazoxanide-treated cells