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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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N1-guanyl-1,7-diaminoheptane (GC7) alters the expression of doxorubicin-induced epithelial–mesenchymal transition (EMT) markers in bladder cancer cells. Phase-contrast microscopic images (a), Western blot analyses of expression of EMT markers (E-cadherin and vimentin), and EMT-associated transcription factors (Twist-1, Zeb-1, and snail) (b), and immunofluorescent images of EMT markers (c) in control bladder cancer cells and bladder cancer cells treated for 48 h with doxorubicin alone, GC7 alone, or doxorubicin plus GC7. (d) Activity of eukaryotic translation initiation factor 5A2 (eIF5A2) was measured by fluorography through detection of newly synthesized hypusinated eIF5A2 in bladder cancer cells treated with doxorubicin (Dox), doxorubicin plus GC7, or vehicle.
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fig03: N1-guanyl-1,7-diaminoheptane (GC7) alters the expression of doxorubicin-induced epithelial–mesenchymal transition (EMT) markers in bladder cancer cells. Phase-contrast microscopic images (a), Western blot analyses of expression of EMT markers (E-cadherin and vimentin), and EMT-associated transcription factors (Twist-1, Zeb-1, and snail) (b), and immunofluorescent images of EMT markers (c) in control bladder cancer cells and bladder cancer cells treated for 48 h with doxorubicin alone, GC7 alone, or doxorubicin plus GC7. (d) Activity of eukaryotic translation initiation factor 5A2 (eIF5A2) was measured by fluorography through detection of newly synthesized hypusinated eIF5A2 in bladder cancer cells treated with doxorubicin (Dox), doxorubicin plus GC7, or vehicle.

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.


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)

N1-guanyl-1,7-diaminoheptane (GC7) alters the expression of doxorubicin-induced epithelial–mesenchymal transition (EMT) markers in bladder cancer cells. Phase-contrast microscopic images (a), Western blot analyses of expression of EMT markers (E-cadherin and vimentin), and EMT-associated transcription factors (Twist-1, Zeb-1, and snail) (b), and immunofluorescent images of EMT markers (c) in control bladder cancer cells and bladder cancer cells treated for 48 h with doxorubicin alone, GC7 alone, or doxorubicin plus GC7. (d) Activity of eukaryotic translation initiation factor 5A2 (eIF5A2) was measured by fluorography through detection of newly synthesized hypusinated eIF5A2 in bladder cancer cells treated with doxorubicin (Dox), doxorubicin plus GC7, or vehicle.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig03: N1-guanyl-1,7-diaminoheptane (GC7) alters the expression of doxorubicin-induced epithelial–mesenchymal transition (EMT) markers in bladder cancer cells. Phase-contrast microscopic images (a), Western blot analyses of expression of EMT markers (E-cadherin and vimentin), and EMT-associated transcription factors (Twist-1, Zeb-1, and snail) (b), and immunofluorescent images of EMT markers (c) in control bladder cancer cells and bladder cancer cells treated for 48 h with doxorubicin alone, GC7 alone, or doxorubicin plus GC7. (d) Activity of eukaryotic translation initiation factor 5A2 (eIF5A2) was measured by fluorography through detection of newly synthesized hypusinated eIF5A2 in bladder cancer cells treated with doxorubicin (Dox), doxorubicin plus GC7, or vehicle.
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.

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