MP34-06 GMCSF GENE THERAPY AND SIRNA TARGETING COX-2 IN A MURINE MODEL OF BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 2014MP34-06 GMCSF GENE THERAPY AND SIRNA TARGETING COX-2 IN A MURINE MODEL OF BLADDER CANCER Sin Mun Tham, Kesavan Esuvaranathan, and Ratha Mahendran Sin Mun ThamSin Mun Tham More articles by this author , Kesavan EsuvaranathanKesavan Esuvaranathan More articles by this author , and Ratha MahendranRatha Mahendran More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder cancer is a good model for gene therapy as candidate genes can be transferred directly to the tumor without surgical intervention. Different cytokine genes successfully induced tumor regression in murine models of bladder cancer. In our studies, intravesical gene therapy with either Granulocyte-Macrophage Colony-Stimulating Factor (GMCSF) or siRNA targeting Cox-2 (Cyclooxygenase-2) (siCox2) successfully cured some mice. This study investigates the efficacy of combined therapy in an orthotopic bladder cancer model. METHODS C57BL/6 mice with bladder tumors received liposome-mediated GMCSF (2.5μg) and siCox2 (1μM/mouse) twice a week for 3 weeks for a total of 6 treatments. As controls, mice received each of these therapies singly as well as saline and non-targeting siRNA (siCon). After 28 days, bladders were harvested, weighed and gene expression changes were analyzed by polymerase chase reaction (PCR). RESULTS 30-33% of mice were cured of bladder tumors with intravesical GMCSF or siCox2 therapy. Local therapy with siCox2 alone resulted in significantly smaller tumors and better survival rates. Mice that were cured after receiving siCox2 therapy showed significant increase in activin receptor-like kinase 7 (Alk7), CD4 and angiotensin II receptor 2 (Agtr2). However, GMCSF therapy did not have an additive effect on the therapeutic effects of siCox2. Few gene expression changes were observed between combined GMCSF and siCox2 against GMCSF and siCon, in which significant increase was observed only in CD4. CONCLUSIONS While local therapy with GMCSF gene therapy or silencing of Cox2 with siRNA have anti-tumor activity individually against bladder cancer in mice, combined therapy did not enhance the beneficial effects. More candidate genes have to be studied to find synergistic anti-tumour effects against bladder cancer. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e364 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Sin Mun Tham More articles by this author Kesavan Esuvaranathan More articles by this author Ratha Mahendran More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...