N1-guanyl-1,7-diaminoheptane sensitizes bladder cancer cells to doxorubicin by preventing epithelial-mesenchymal transition through inhibition of eukaryotic translation initiation factor 5A2 activation.
Bottom Line: Drug resistance greatly reduces the efficacy of doxorubicin-based chemotherapy in bladder cancer treatment; however, the underlying mechanisms are poorly understood.It significantly inhibited activity of eIF5A2, suppressed doxorubicin-induced epithelial-mesenchymal transition in BIU-87 cells, and promoted mesenchymal-epithelial transition in J82 and UM-UC-3 cells.Combination therapy with GC7 may enhance the therapeutic efficacy of doxorubicin in bladder cancer by inhibiting eIF5A2 activation and preventing epithelial-mesenchymal transition.
Affiliation: Department of Radiation Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.Show MeSH
Related in: MedlinePlus
Mentions: To further ascertain if the phenotype of the bladder cancer cells contributed to their differing chemosensitivity to the combined therapy, we examined morphology and measured the expression of epithelial/mesenchymal markers in bladder cancer cells. In the views of phase-contrast microscopy, BIU-87 cells showed tight cell–cell adhesion and cobblestone-like colony characters, whereas J82 and UM-UC-3 cells were spindle-like, more flattened, and had lost the majority of cell contacts (Fig. 3a). The E-cadherin/vimentin ratio was clearly higher in BIU-87 cells with an epithelial phenotype than in the J82 and UM-UC-3 cells, which have a mesenchymal phenotype (Fig. 3b). Therefore, the ability of GC7 to enhance the cytotoxicity of doxorubicin did not occur in relation to phenotype transition in bladder cancer cells.
Affiliation: Department of Radiation Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.