Anti-cancer effects of nitazoxanide in epithelial ovarian cancer in-vitro and in-vivo

Abstract

Epithelial ovarian cancer is one of the most lethal gynecologic malignancies and poses a considerable threat to women's health. Although the progression-free survival of patients has been prolonged with the application of anti-angiogenesis drugs and Poly (ADP-ribose) polymerases (PARP) inhibitors, overall survival has not substantially improved. Thus, new therapeutic strategies are essential for the treatment of ovarian cancer. Nitazoxanide (NTZ), an FDA-approved anti-parasitic drug, has garnered attention for its potential anti-cancer activity. However, the anti-tumor effects and possible underlying mechanisms of NTZ on ovarian cancer remain unclear. In this study, we investigated the anti-tumor effects and the mechanism of NTZ on ovarian cancer in vitro and in vivo. We found that NTZ inhibited the proliferation of A2780 and SKOV3 epithelial ovarian cancer cells in a time- and concentration-dependent manner; Furthermore, NTZ suppressed the metastasis and invasion of A2780 and SKOV3 cells in vitro, correlating with the inhibition of epithelial-mesenchymal transition; Additionally, NTZ suppressed the Hippo/YAP/TAZ signaling pathway both in vitro and in vivo and demonstrated a good binding activity with core genes of Hippo pathway, including Hippo, YAP, TAZ, LATS1, and LATS2. Oral administration of NTZ inhibited tumor growth in xenograft ovarian cancer mice models without causing considerable damage to major organs. Overall, these data suggest that NTZ has therapeutic potential for treating epithelial ovarian cancer.