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• W2051278488 abstract "You have accessJournal of UrologyBladder Cancer: Basic Research II1 Apr 2010974 TRICHOSTATIN A MEDIATED RESENSITIZATION OF CHEMO-RESISTANT T24R2 HUMAN BLADDER CANCER CELL LINE TO CISPLATIN Cheol Yong Yoon, Mi Jung Park, Seung Whan Doo, Hong Zoo Park, Dae Sung Kim, Won Ki Lee, Seong Jin Jeong, Sung Kyu Hong, Seok Soo Byun, Eun Sik Lee, and Sang Eun Lee Cheol Yong YoonCheol Yong Yoon More articles by this author , Mi Jung ParkMi Jung Park More articles by this author , Seung Whan DooSeung Whan Doo More articles by this author , Hong Zoo ParkHong Zoo Park More articles by this author , Dae Sung KimDae Sung Kim More articles by this author , Won Ki LeeWon Ki 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 , Eun Sik LeeEun Sik 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.2010.02.1921AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Trichostatin A (TSA) is a potent inhibitor of the mammalian class I and II histone deacetylase (HDAC) families and histone deacetylase inhibitors (HDI) like TSA have been reported to inhibit the growth and survival of tumors including breast, prostate, ovarian and colon cancers. In this study we explored TSA mediated resensitization of cisplatin-resistant human bladder cancer cell line T24R2 and related mechanisms. METHODS Invasive human bladder cancer cell line T24R2 having resistance to cisplatin (up to 2ug/ml) has been treated with increasing dose of TSA (0.05-1.0uM) alone or in combination with cisplatin (0.313ug/ml-20ug/ml) for 48-72h and anti-tumor effect was assessed with CCK-8 and clonogenic assay. Alterations in cell cycle and apoptosis were determined by flow cytometric analysis and Hoechst33342 staining. Caspase 3, 8, 9, p-Akt, and t-Akt expression was evaluated by immunoblotting. RESULTS Cytotoxicity and colony forming assays showed synergistic anti-tumor effect between TSA and cisplatin against T24R2 cell. TSA sensitized T24R2 cell to cisplatin in a dose- and time-dependent manner and at the presence of TSA, T24R2 fully restored sensitivity to cisplatin up to similar level of T24. Combined treatment of T24R2 with cisplatin and TSA caused increase in sub-G1 and S phase cell population which was accompanied by the increase in the activity of caspase 3, 8, and 9 and down-regulation of p-Akt / t-Akt. Hoechst33342 staining showed marked increase of apoptotic-body formation in T24R2 cell treated with cisplatin and TSA together,compared to control and cisplatin or TSA single treated cases. CONCLUSIONS These findings show that TSA synergistically restores sensitivity to cisplatin in cheomo-resistant human bladder cancer cells through the activation of caspase-dependent apoptotic pathway and also down-regulation of Akt survival pathway. Taken together, these results suggest the possibility of novel HDI and cisplatin based combined chemo-regimens to enhance anti-tumor effect of cisplain in invasive human bladder cancers. Seongnam, Republic of Korea© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e378-e379 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cheol Yong Yoon More articles by this author Mi Jung Park More articles by this author Seung Whan Doo More articles by this author Hong Zoo Park More articles by this author Dae Sung Kim More articles by this author Won Ki 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 Eun Sik Lee More articles by this author Sang Eun Lee More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W2051278488 title "974 TRICHOSTATIN A MEDIATED RESENSITIZATION OF CHEMO-RESISTANT T24R2 HUMAN BLADDER CANCER CELL LINE TO CISPLATIN" @default.
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