MP21-15 ANTITUMOR ACTIVITY OF C-MYC INHIBITOR KSI-3716 IN A GEMCITABINE-RESISTANT BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2014MP21-15 ANTITUMOR ACTIVITY OF C-MYC INHIBITOR KSI-3716 IN A GEMCITABINE-RESISTANT BLADDER CANCER Ho Kyung Seo, Whi-An Kwon, Dong Wan Sohn, Jeong Hwan Son, Weon Seo Park, Kang-Hyun Lee, Sang-Jin Lee, and Kyung-Chae Jeong Ho Kyung SeoHo Kyung Seo More articles by this author , Whi-An KwonWhi-An Kwon More articles by this author , Dong Wan SohnDong Wan Sohn More articles by this author , Jeong Hwan SonJeong Hwan Son More articles by this author , Weon Seo ParkWeon Seo Park More articles by this author , Kang-Hyun LeeKang-Hyun Lee More articles by this author , Sang-Jin LeeSang-Jin Lee More articles by this author , and Kyung-Chae JeongKyung-Chae Jeong More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.843AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To investigate the functional role of c-Myc during the development of gemcitabine resistance and further to evaluate the efficacy of a c-Myc inhibitor, KSI-3716 against gemcitabine-resistant bladder cancer cells. METHODS The cytotoxicity of gemcitabine was evaluated in vivo and in vitro in several bladder cancer cell lines and KU19-19 xenografts in nude mice. Long-term in vitro exposure to gemcitabine induced gemcitabine-specific resistance. Gemcitabine-resistant cells, termed KU19-19/GEM, formed xenograft tumors even in the presence of 2 mg/kg gemcitabine. Action of c-Myc inhibitor, KSI-3716 was assessed by Cell cycle analysis, detection of apoptosis using TUNEL assay and cytotoxicity using 5-ethynyl-20-deoxyuridine (EdU)incorporation assay. RESULTS Gemcitabine effectively suppressed proliferation in several bladder cancer cell lines and growth of KU19-19 xenografts in nude mice, although all mice relapsed later. KU19-19/GEM expressed more c-Myc proteins by 30% in the presence of gemcitabine. KSI-3716 inhibited cell survival by 85% at 2 uM in KU19-19/GEM. The sequential addition of gemcitabine and KSI-3716 inhibited gemcitabine-resistant cell proliferation to a great extent than each drug alone. (Figure 1). CONCLUSIONS These results suggest that sequential treatment with gemcitabine and KSI-3716 may be beneficial to bladder cancer patients. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e231 Peer Review Report Advertisement Copyright & Permissions© 2014MetricsAuthor Information Ho Kyung Seo More articles by this author Whi-An Kwon More articles by this author Dong Wan Sohn More articles by this author Jeong Hwan Son More articles by this author Weon Seo Park More articles by this author Kang-Hyun Lee More articles by this author Sang-Jin Lee More articles by this author Kyung-Chae Jeong More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...