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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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Cytotoxicity of doxorubicin or doxorubicin plus N1-guanyl-1,7-diaminoheptane (GC7) in bladder cancer cells. GC7 (50 μM) significantly enhanced the cytotoxicity of doxorubicin in BIU-87 (a), J82 (b), and UM-UC-3 (c) cells. Solid and dashed lines denote the best fit and 95% confidence intervals, respectively, of the different treatments. Photomicrographs and bar charts depict the 5-ethynyl-2′-deoxyuridine (EdU) staining pattern and relative EdU-positive ratio, respectively, of BIU-87 (d), J82 (e), and UM-UC-3 (f) cells after 48 h of treatment with doxorubicin or doxorubicin plus GC7. ***P < 0.001.
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fig02: Cytotoxicity of doxorubicin or doxorubicin plus N1-guanyl-1,7-diaminoheptane (GC7) in bladder cancer cells. GC7 (50 μM) significantly enhanced the cytotoxicity of doxorubicin in BIU-87 (a), J82 (b), and UM-UC-3 (c) cells. Solid and dashed lines denote the best fit and 95% confidence intervals, respectively, of the different treatments. Photomicrographs and bar charts depict the 5-ethynyl-2′-deoxyuridine (EdU) staining pattern and relative EdU-positive ratio, respectively, of BIU-87 (d), J82 (e), and UM-UC-3 (f) cells after 48 h of treatment with doxorubicin or doxorubicin plus GC7. ***P < 0.001.

Mentions: To assess the synergistic cytotoxic effect of doxorubicin plus GC7, we used the CCK8 assay to measure cell viability and EdU incorporation assay to test the inhibition of proliferation of bladder cancer cells treated for 48 h with doxorubicin alone or doxorubicin plus GC7. BIU-87 cells showed a higher sensitivity to doxorubicin than J82 and UM-UC-3 cells (Fig. 2). The IC50 of doxorubicin at 48 h in BIU-87, J82, and UM-UC-3 cells was 0.38, 0.77, and 0.76 μg/mL, respectively (Table 1). Cotreatment with GC7 significantly increased doxorubicin-induced cytotoxicity in all cell lines (Fig. 2, Table 1). Hence, GC7 significantly sensitized bladder cancer cells to doxorubicin.


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)

Cytotoxicity of doxorubicin or doxorubicin plus N1-guanyl-1,7-diaminoheptane (GC7) in bladder cancer cells. GC7 (50 μM) significantly enhanced the cytotoxicity of doxorubicin in BIU-87 (a), J82 (b), and UM-UC-3 (c) cells. Solid and dashed lines denote the best fit and 95% confidence intervals, respectively, of the different treatments. Photomicrographs and bar charts depict the 5-ethynyl-2′-deoxyuridine (EdU) staining pattern and relative EdU-positive ratio, respectively, of BIU-87 (d), J82 (e), and UM-UC-3 (f) cells after 48 h of treatment with doxorubicin or doxorubicin plus GC7. ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Cytotoxicity of doxorubicin or doxorubicin plus N1-guanyl-1,7-diaminoheptane (GC7) in bladder cancer cells. GC7 (50 μM) significantly enhanced the cytotoxicity of doxorubicin in BIU-87 (a), J82 (b), and UM-UC-3 (c) cells. Solid and dashed lines denote the best fit and 95% confidence intervals, respectively, of the different treatments. Photomicrographs and bar charts depict the 5-ethynyl-2′-deoxyuridine (EdU) staining pattern and relative EdU-positive ratio, respectively, of BIU-87 (d), J82 (e), and UM-UC-3 (f) cells after 48 h of treatment with doxorubicin or doxorubicin plus GC7. ***P < 0.001.
Mentions: To assess the synergistic cytotoxic effect of doxorubicin plus GC7, we used the CCK8 assay to measure cell viability and EdU incorporation assay to test the inhibition of proliferation of bladder cancer cells treated for 48 h with doxorubicin alone or doxorubicin plus GC7. BIU-87 cells showed a higher sensitivity to doxorubicin than J82 and UM-UC-3 cells (Fig. 2). The IC50 of doxorubicin at 48 h in BIU-87, J82, and UM-UC-3 cells was 0.38, 0.77, and 0.76 μg/mL, respectively (Table 1). Cotreatment with GC7 significantly increased doxorubicin-induced cytotoxicity in all cell lines (Fig. 2, Table 1). Hence, GC7 significantly sensitized bladder cancer cells to doxorubicin.

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