596 A NOVEL AND EFFICIENT GENE THERAPY FOR THE TREATMENT OF UROTHELIAL CARCINOMA

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research (I)1 Apr 2013596 A NOVEL AND EFFICIENT GENE THERAPY FOR THE TREATMENT OF UROTHELIAL CARCINOMA Eduardo Landerer, Maximiliano Bendek, Lorena Lobos, Miguel Ávila, Alexis Rivas, Vincenzo Borgna, Luis O. Burzio, Carlos González, and Jaime Villegas Eduardo LandererEduardo Landerer Santiago, Chile More articles by this author , Maximiliano BendekMaximiliano Bendek Santiago, Chile More articles by this author , Lorena LobosLorena Lobos Santiago, Chile More articles by this author , Miguel ÁvilaMiguel Ávila Santiago, Chile More articles by this author , Alexis RivasAlexis Rivas Santiago, Chile More articles by this author , Vincenzo BorgnaVincenzo Borgna Santiago, Chile More articles by this author , Luis O. BurzioLuis O. Burzio Santiago, Chile More articles by this author , Carlos GonzálezCarlos González Santiago, Chile More articles by this author , and Jaime VillegasJaime Villegas Santiago, Chile More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1992AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The epidemiological data related to bladder cancer recurrence and mortality, support the need of novel therapeutic approaches in order to avoid recurrence, invasion and improve the survival rate and the quality of life of patients diagnosed as having this neoplasm. In the early 2000, our laboratory described the existence of a novel family of non-coding mitochondrial RNAs (ncmtRNAs), named Sense (S-ncmtRNA) and Antisense (AS-ncmtRNA). Lipofection of antisense oligodeoxynucleotides (AS-ODN) full phosphorotioate (PS), complementary to the human AS-ncmtRNA on HeLa cells, in vitro, induces cell death. Interestingly, similar treatment does not affect the viability of cultures of normal cell lines such us human keratinocytes. Aim To demonstrate that the transfection of AS-ODN complementary to the AS-ncmtRNA on bladder cancer cell lines represent a novel and efficient gene therapy for the treatment of urothelial carcinoma. METHODS Murine cell lines: The murine bladder cancer cell line MB49 were harvested at 60% of confluence, and lipofected in optimem (serum an antibiotic free) for 6 hours with 200 nM full PS AS-ODN complementary to the murine AS-ncmtRNA. Afterwards, the original culture medium was re-established, and the cells were incubated at 37° C, 5% CO2 in humidity chamber, for 48 hrs. We analysed cell viability; migration, invasion and wound healing capabilities. We used normal urothelial cells obtained as primary culture from wild type C57/Bl 6 mice like control, carrying out the same protocol described above. Human cell lines: The human bladder cancer cells line RT-4, T24 and UM-UC3 were harvested at 60% of confluence, and lipofected in optimem (serum an antibiotic free) for 6 hours with 200 nM full PS AS-ODN complementary to the murine AS-ncmtRNA. Afterwards, the original culture medium was re-established, and the cells were incubated at 37° C, 5% CO2 in humidity chamber, for 48 hrs. We analysed cell viability; migration, invasion and wound healing capabilities. RESULTS The treatment of all the bladder cancer cell lines described with AS ODN complementary to the ASncmtRNAs (human or murine) caused massive cell death, decreased proliferative capacity and diminished wound healing closure compared with those treated with a control AS-ODN and non-treated cells. Furthermore, in normal cells, the same treatment did not affect their viability. CONCLUSIONS Taken together, these results demonstrate that: 1 The AS-ncmtRNA is a suitable target for a new therapeutic strategy for bladder cancer. 2 The use of this approach can be evaluated in a murine (in vivo) bladder cancer model. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e243-e244 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eduardo Landerer Santiago, Chile More articles by this author Maximiliano Bendek Santiago, Chile More articles by this author Lorena Lobos Santiago, Chile More articles by this author Miguel Ávila Santiago, Chile More articles by this author Alexis Rivas Santiago, Chile More articles by this author Vincenzo Borgna Santiago, Chile More articles by this author Luis O. Burzio Santiago, Chile More articles by this author Carlos González Santiago, Chile More articles by this author Jaime Villegas Santiago, Chile More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...