Inhibition of Notch pathway enhances the anti-tumor effect of docetaxel in prostate cancer stem-like cells [post]

Lei Wang, Hao Zi, Yi Luo, Tongzu Liu, Hang Zheng, Conghua Xie, Xinghuan Wang, Xing Huang
2020 unpublished
Background: Prostate cancer stem-like cells (PCSCs) likely participate in tumor progression and recurrence, and demonstrate resistance to chemotherapy. The Notch pathway plays a role in the maintenance of the stemness in PCSCs. This study aimed to investigate the efficacy of Notch signaling inhibition as an adjuvant to docetaxel (DOX) in PCSCs.Methods: PCSCs derived from PC-3 cell line were examined for Notch-1 expression. The effect of Notch inhibition on response to DOX was evaluated in PCSCs
more » ... evaluated in PCSCs in vitro and in murine models using a γ-secretase inhibitor (GSI), PF-03084014. Impacts on cell proliferation, apoptosis, cell cycle, and sphere formation were evaluated.Results: PC-3 PCSCs expressed elevated Notch-1 mRNA compared with PC-3 parental cells. The combination of GSI with DOX promoted DOX induced cell growth inhibition, apoptosis, cell cycle arrest, and sphere formation in PCSCs. In nude mice bearing PC-3 PCSCs-derived tumors, the combination of GSI and DOX reduced the tumor growth, which was associated with the decreased Notch-1 expression in tumor tissues.Conclusions: These results reveal that inhibition of Notch pathway enhances the anti-tumor effect of DOX in PC-3 PCSCs, and suggest that Notch inhibition may have clinical benefits in targeting PCSCs.
doi:10.21203/rs.3.rs-17013/v2 fatcat:cci3mdjmkveqzgaw5scjdurfui