MP39-05 SYNERGISTIC ANTITUMOR EFFECT OF SAHA AND CISPLATIN IN CISPLATIN RESISTANT BLADDER CANCER CELL LINE

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research IV1 Apr 2014MP39-05 SYNERGISTIC ANTITUMOR EFFECT OF SAHA AND CISPLATIN IN CISPLATIN RESISTANT BLADDER CANCER CELL LINE Ha Rim Kook, Young Ju Lee, Jae Seung Yeon, Han Sol Lee, Choong Hee Noh, Kwang Mo Kim, Ki Beom Kim, Jung Keun Lee, Sangchul Lee, Seong Jin Jeong, Sung Kyu Hong, Seok-Soo Byun, Eunsik Lee, and Sang Eun Lee Ha Rim KookHa Rim Kook More articles by this author , Young Ju LeeYoung Ju Lee More articles by this author , Jae Seung YeonJae Seung Yeon More articles by this author , Han Sol LeeHan Sol Lee More articles by this author , Choong Hee NohChoong Hee Noh More articles by this author , Kwang Mo KimKwang Mo Kim More articles by this author , Ki Beom KimKi Beom Kim More articles by this author , Jung Keun LeeJung Keun Lee More articles by this author , Sangchul LeeSangchul Lee More articles by this author , Seong Jin JeongSeong Jin Jeong More articles by this author , Sung Kyu HongSung Kyu Hong More articles by this author , Seok-Soo ByunSeok-Soo Byun More articles by this author , Eunsik LeeEunsik Lee More articles by this author , and Sang Eun LeeSang Eun Lee More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1320AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cisplatin-based chemotherapy remains first-line treatment for advanced bladder cancer. No standard chemotherapeutic agent has been established for patients with cisplatin resistant bladder cancer. We investigated the synergistic antitumor effect of of suberoylanilide hydroxamic acid (SAHA) and cisplatin in cisplatin resistant bladder cancer cells (T24R2). METHODS The cisplatin resistant human bladder cancer cell line (T24R2) was treated with cisplatin and/or SAHA. Tumor cell proliferation was assessed by cell counting kit-8 assay and clonogenic assay. Synergism was determined by combination index. Changes in cell cycle were determined by flow cytometry. Expression of caspase-3, 8 and 9, PARP, cytochrome c, p21, Bcl-2, Bad, p27, cyclin A, cyclin D1, and cyclin E were analyzed by Western blotting. RESULTS Synergistic antitumor effect between cisplatin and SAHA was observed by cell counting kit-8 assay, clonogenic assay and confirmed with combination index less than 1.0. The underlying mechanism could be synergistic cell cycle arrest, activation of apoptotic pathway including capase-3, -8, -9 and fragmented PARP or decreased expression in anti-apoptotic Bcl-2 and increased expression in pro-apoptotic BAD. CONCLUSIONS SAHA may synergistically enhancethe antitumor effect of cisplatin and resensitize cisplatin resistant bladder cancer cells. These findings suggest the potential use of SAHA as a combination agent to enhance the antitumor effect of cisplatin in patients with advanced bladder cancer. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e427-e428 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Ha Rim Kook More articles by this author Young Ju Lee More articles by this author Jae Seung Yeon More articles by this author Han Sol Lee More articles by this author Choong Hee Noh More articles by this author Kwang Mo Kim More articles by this author Ki Beom Kim More articles by this author Jung Keun Lee More articles by this author Sangchul Lee More articles by this author Seong Jin Jeong More articles by this author Sung Kyu Hong More articles by this author Seok-Soo Byun More articles by this author Eunsik Lee More articles by this author Sang Eun Lee More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...