Deferasirox Shows Inhibition Activity Against Cervical Cancer in vitro and in vivo [post]

Nan Zhou, Yan Cui, Yuhuan Kuang, Jianyuan Hou, Yumeng Zhu, ShuBo Chen, Xin Xu, Ke Tan, Pengxiu Cao, Xianglin Duan, Fan yumei
2020 unpublished
Background: Iron depletion may be a novel therapeutic strategy for cancer. As an oral iron chelator, deferasirox (DFX) is expected to become an anticancer agent. This study aimed to assess the effects of DFX on cervical cancer.Methods: The effects of DFX on cellular iron metabolism, cell viability, cell cycle and apoptosis, and cell invasion were assessed in two cervical cancer cell lines. The effects of DFX on the expression of cell cycle regulators cyclin D1, cyclin E and proliferating cell
more » ... clear antigen (PCNA) were examined. The expression of N-myc downstream regulated gene 1 (NDRG1) and c-myc, and the activation of the MEK/ERK signaling pathway were investigated. The effect of DFX on tumor burden was assessed using a murine xenograft model.Results: DFX decreased the viability of HeLa and SiHa cells, induced cell cycle and apoptosis, and decreased cell invasion. The expression of NDRG1 was upregulated while that of c-myc was downregulated. The activation of the MEK/ERK signaling pathway was inhibited by DFX. DFX also significantly suppressed xenograft tumor growth with no serious side effects, decreased ferritin levels in nude mice serum, and decreased ferritin heavy chain (FTH) expression in xenograft tumor tissue.Conclusions: The inhibitory effect of DFX on cervical cancer cells and xenograft tumor growth was related to its effective depletion of iron in tumor cells. These results demonstrate that DFX has potential as a therapeutic agent for cervical cancer.
doi:10.21203/ fatcat:donymg65ifgxpebcxygqogm7ui