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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.

Yang J, Yu H, Shen M, Wei W, Xia L, Zhao P - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

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Effects of Twist-1 siRNA on expression levels of epithelial–mesenchymal transition markers and sensitivity to doxorubicin treatment in bladder cancer cells. Phase-contrast microscopic images (a) and Western blot analyses (b) of expression of epithelial–mesenchymal transition markers in doxorubicin-treated Twist-1 or negative siRNA-transfected bladder cancer cells. (c) Cytotoxicity of doxorubicin in Twist-1 or negative siRNA-transfected bladder cancer cells. Solid and dashed lines denote the best fit and 95% confidence intervals, respectively, of the different treatments.
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fig04: Effects of Twist-1 siRNA on expression levels of epithelial–mesenchymal transition markers and sensitivity to doxorubicin treatment in bladder cancer cells. Phase-contrast microscopic images (a) and Western blot analyses (b) of expression of epithelial–mesenchymal transition markers in doxorubicin-treated Twist-1 or negative siRNA-transfected bladder cancer cells. (c) Cytotoxicity of doxorubicin in Twist-1 or negative siRNA-transfected bladder cancer cells. Solid and dashed lines denote the best fit and 95% confidence intervals, respectively, of the different treatments.

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.


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.

Yang J, Yu H, Shen M, Wei W, Xia L, Zhao P - Cancer Sci. (2014)

Effects of Twist-1 siRNA on expression levels of epithelial–mesenchymal transition markers and sensitivity to doxorubicin treatment in bladder cancer cells. Phase-contrast microscopic images (a) and Western blot analyses (b) of expression of epithelial–mesenchymal transition markers in doxorubicin-treated Twist-1 or negative siRNA-transfected bladder cancer cells. (c) Cytotoxicity of doxorubicin in Twist-1 or negative siRNA-transfected bladder cancer cells. Solid and dashed lines denote the best fit and 95% confidence intervals, respectively, of the different treatments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317814&req=5

fig04: Effects of Twist-1 siRNA on expression levels of epithelial–mesenchymal transition markers and sensitivity to doxorubicin treatment in bladder cancer cells. Phase-contrast microscopic images (a) and Western blot analyses (b) of expression of epithelial–mesenchymal transition markers in doxorubicin-treated Twist-1 or negative siRNA-transfected bladder cancer cells. (c) Cytotoxicity of doxorubicin in Twist-1 or negative siRNA-transfected bladder cancer cells. Solid and dashed lines denote the best fit and 95% confidence intervals, respectively, of the different treatments.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Show MeSH
Related in: MedlinePlus