Traditional Chinese Medicine Science Research Funds Program of Zhejiang (2013ZA077); Natural Science Funds of Zhejiang (Y2110555); National 973 Basic Research Program of China (2013CB911300).
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
Article first published online: 7 JAN 2014
© 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Volume 105, Issue 2, pages 219–227, February 2014
How to Cite
Cancer Sci 105 (2014) 219–227
- Issue published online: 10 FEB 2014
- Article first published online: 7 JAN 2014
- Accepted manuscript online: 22 NOV 2013 12:14AM EST
- Manuscript Accepted: 17 NOV 2013
- Manuscript Revised: 11 NOV 2013
- Manuscript Received: 14 JUL 2013
- Traditional Chinese Medicine Science Research Funds Program of Zhejiang. Grant Number: 2013ZA077
- Natural Science Funds of Zhejiang. Grant Number: Y2110555
- National 973 Basic Research Program of China. Grant Number: 2013CB911300
- drug resistance;
- epithelial–mesenchymal transition;
- eukaryotic translation initiation factor 5A;
- urinary bladder neoplasms
Drug resistance greatly reduces the efficacy of doxorubicin-based chemotherapy in bladder cancer treatment; however, the underlying mechanisms are poorly understood. We aimed to investigate whether N1-guanyl-1,7-diaminoheptane (GC7), which inhibits eukaryotic translation initiation factor 5A2 (eIF5A2) activation, exerts synergistic cytotoxicity with doxorubicin in bladder cancer, and whether eIF5A2 is involved in chemoresistance to doxorubicin-based bladder cancer treatment. BIU-87, J82, and UM-UC-3 bladder cancer cells were transfected with eIF5A2 siRNA or negative control siRNA before incubation with doxorubicin alone or doxorubicin plus GC7 for 48 h. Doxorubicin cytotoxicity was enhanced by GC7 in BIU-87, J82, and UM-UC-3 cells. 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. Knockdown of eIF5A2 sensitized bladder cancer cells to doxorubicin, prevented doxorubicin-induced EMT in BIU-87 cells, and encouraged 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.