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• W2796383954 abstract "You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II1 Apr 2018MP72-12 CO-TREATMENT WITH L-METHADONE INCREASES THE EFFICACY OF ANTITUMOR AGENTS IN RENAL CELL CARCINOMA CELLS IN VITRO Birgit Stadlbauer, Heike Pohla, Christian Stief, and Alexander Buchner Birgit StadlbauerBirgit Stadlbauer More articles by this author , Heike PohlaHeike Pohla More articles by this author , Christian StiefChristian Stief More articles by this author , and Alexander BuchnerAlexander Buchner More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2296AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In leukemia and glioblastoma cells, a significant increase of apoptosis rates was observed in vitro under cytostatic therapy by activation of the μ-opioid receptor with methadone. This study investigated the effect of methadone co-treatment in renal cell carcinoma (RCC) cells in the presence of different antitumor agents. METHODS The clear-cell RCC cell line RCC-26 was incubated with different antitumor drugs (doxorubicin, mitoxantrone, axitinib and others). The ratio of cells in apoptosis after 5 days was analyzed using flow cytometry with annexin V-APC and 7AAD double staining. In each setting, the cells were co-incubated with various concentrations of L-methadone and D,L-methadone (0-30μg/ml). The opioid antagonist naloxone served as negative control. Additionally, cell proliferation assays (Cell Titer 96 AQueous One Solution, Promega) and cell migration assays (Automated Cellular Analysis System, MetaVi Labs) were conducted. Furthermore, gene expression analysis including pathway analysis was performed using microarrays (Affymetrix GeneChip Prime View with ca. 49,000 transcripts) to reveal changes in cell biology caused by methadone co-treatment. RESULTS Incubation of RCC-26 cells with 1μM doxorubicin resulted in 32% apoptosis after 5 days. Co-incubation with L-methadone showed a dose-dependent increase of apoptosis rate up to 78% (2.4-fold increase). The effect of D,L-methadone was similar but less pronounced. Control experiments with naloxone instead of methadone showed no influence on the apoptosis rate. Comparable results were achieved with other tumor cell lines, e.g. A172 glioblastoma cells. RCC-26 proliferation was significantly decreased by co-incubation with L-methadone and doxorubicin vs. one of these drugs alone. Cell migration assays showed a complete inhibition of RCC-26 migration by co-incubation with 10ng/ml L-methadone and 1μM doxorubicin. Microarray analysis identified 333 upregulated and 69 downregulated genes (≥2-fold change of expression level, p<0.05) caused by L-methadone in RCC-26 cells. CONCLUSIONS Co-incubation with L-methadone enhances the therapeutic effect of antitumor drugs in renal cell carcinoma cells and in various other tumor cell lines. The increase of the cytostatic effect depends on the combination of cell line and antitumor agent. The combination of L-methadone with certain antitumor drugs might be a promising new approach to increase the therapeutic efficacy in renal cell carcinoma. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e956 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Birgit Stadlbauer More articles by this author Heike Pohla More articles by this author Christian Stief More articles by this author Alexander Buchner More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W2796383954 title "MP72-12 CO-TREATMENT WITH L-METHADONE INCREASES THE EFFICACY OF ANTITUMOR AGENTS IN RENAL CELL CARCINOMA CELLS IN VITRO" @default.
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