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: In order to ascertain the roles of EMT in doxorubicin sensitivity in bladder cancer cells, we examined the effect of doxorubicin on Twist-1 siRNA-treated bladder cancer cells. According to morphologic changes, Twist-1 siRNA-transfected BIU87 cells sustained the epithelial phenotype during doxorubicin treatment compared to the negative control (Fig. 4a). In line with these observations, Twist-1 siRNA reversed doxorubicin-induced changes of E-cadherin and vimentin in BIU-87 cells (Fig. 4b). These results indicated that Twist-1 siRNA reversed doxorubicin-induced EMT. Next, we explored the sensitivity change to doxorubicin in Twist-1 siRNA-treated BIU-87 cells and found that Twist-1 siRNA significantly enhanced the cytotoxicity of doxorubicin (Fig. 4c, Table 2). Hence, doxorubicin-induced EMT is a major reason accounting for doxorubicin resistance.
Affiliation: Department of Radiation Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.