MP49-13 LIM-SH3 DOMAIN PROTEIN 1 KNOCKDOWN INHIBITS CELL GROWTH AND ENHANCES ACTIVITY OF CISPLATIN IN BLADDER CANCER.

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 2015MP49-13 LIM-SH3 DOMAIN PROTEIN 1 KNOCKDOWN INHIBITS CELL GROWTH AND ENHANCES ACTIVITY OF CISPLATIN IN BLADDER CANCER. Takashi Dejima, Ario Takeuchi, Tetsutaro Hayashi, Jeffrey Leong, Tabitha Tombe, Kevin Tam, Htoo Oo, Peter Black, Seiji Naito, Martin Gleave, and Christopher Ong Takashi DejimaTakashi Dejima More articles by this author , Ario TakeuchiArio Takeuchi More articles by this author , Tetsutaro HayashiTetsutaro Hayashi More articles by this author , Jeffrey LeongJeffrey Leong More articles by this author , Tabitha TombeTabitha Tombe More articles by this author , Kevin TamKevin Tam More articles by this author , Htoo OoHtoo Oo More articles by this author , Peter BlackPeter Black More articles by this author , Seiji NaitoSeiji Naito More articles by this author , Martin GleaveMartin Gleave More articles by this author , and Christopher OngChristopher Ong More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.517AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder cancer is the 6th most common cancer in the USA. The current standard therapy for the first line of metastatic or local advanced bladder cancer is combination therapy with cisplatin (CDDP) and gemcitabine (GEM). However 5-years survival is still below 50%; therefore additional therapy is needed. LIM-SH3 domain protein 1 (LASP1), identified from cDNA library of metastatic axillary lymph nodes of breast cancer, has been shown to promote cancer progression and invasion in several malignancies. In bladder cancer, LASP1 expression associates with cell invasion and can be used for detecting bladder cancer. However, the anti-tumor effects of LASP1 knockdown in vivo as well as combination therapy with chemotherapy remain unclear. In this study, we investigated the anti-cancer activity of LASP1 knockdown in bladder cancer. METHODS LASP1 gene expression of tumor samples is analyzed using the Affymetrix Exon Array. The LASP1 expression in several bladder cancer cell lines was assessed by Western blot analysis and quantitative reverse transcription-PCR. Silencing of LASP1 in vitro was achieved using siRNA. The In vivo effect of LASP1 antisense oligonucleotide (ASO) treatment was assessed in the T24 CDDP-R (cisplatin-resistant) orthotopic bladder cancer model. RESULTS High LASP1 expression correlated with recurrence rate between patients receiving adjuvant chemotherapy or not. This difference is increased in patients after adjuvant chemotherapy. The LASP1 expression is higher in UC1 and UC15 cells than in UC13 and UC6 cells. Knockdown of LASP1 using siRNA inhibited cell growth, and was accompanied by an increase in p21 and p27. Conversely, stable LASP1 overexpression drove cell growth with increase of cyclinD1 in UC13 and UC6 cells. The treatment of CDDP and GEM induced LASP1 expression in vitro. Combination treatment with LASP1 knockdown using siRNA and CDDP inhibited cell growth in UC1 cells. Furthermore, compared with parental cell line, LASP1 is higher in T24 CDDP-R and RT112 CDDP-R cells than in parental cells. In the orthotopic bladder cancer model, systemic LASP1 ASO administration to athymic nude mice delayed tumor progression in T24 CDDP-R cells. CONCLUSIONS These data revealed that LASP1 inhibition might be as a promising novel therapeutics modality in the treatment of bladder cancer, as well as a possible synergy with chemotherapy. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e607-e608 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takashi Dejima More articles by this author Ario Takeuchi More articles by this author Tetsutaro Hayashi More articles by this author Jeffrey Leong More articles by this author Tabitha Tombe More articles by this author Kevin Tam More articles by this author Htoo Oo More articles by this author Peter Black More articles by this author Seiji Naito More articles by this author Martin Gleave More articles by this author Christopher Ong More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...