Comparison of therapeutic efficacy of lipo-doxorubicin and doxorubicin in treating bladder cancer

Autor: Shun-Hsing Hung, Dah-Shyong Yu, Hui-Yu Yan, Chia-Lun Wu
Rok vydání: 2017
Předmět:
Zdroj: Urological Science, Vol 28, Iss 4, Pp 200-205 (2017)
ISSN: 1879-5226
DOI: 10.1016/j.urols.2016.08.001
Popis: Objectives: Doxorubicin is commonly used in the treatment of superficial bladder cancer, but more side effects and shorter intracellular retention time hamper its clinical application. Since lipo-doxorubicin (Lipodox) has the advantages of longer half-life and lower clearance rate than doxorubicin, it should improve the efficacy of tumor therapy and reduce the normal tissue toxicity of doxorubicin. Materials and Methods: In this study, we compared the cytotoxicity of Lipodox and doxorubicin in different treatment durations on bladder cancer cells by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Drug distribution was tracked under fluorescence microscopy. The metabolic rate after treatment was measured by serial flow cytometry. Finally, an in vivo orthotopic MBT-2 bladder tumor model was established for comparing the differences of therapeutic efficacy, including tumor weight and survival rate. Results: The 50% inhibitory concentration (IC50) of doxorubicin and Lipodox for MBT-2 cells was 0.62 μg/mL and 130 μg/mL, respectively, after 48 hours treatment. Lipo-dox presented higher cytotoxicity than doxorubicin at 6 hours (93% vs 73%) and 12 hours (93% vs 80%) treatment. After drug treatment, Lipodox fluorescence distribution was observed mostly in the cell membrane, lysosomes, and nuclei of tumor cells, while doxorubicin was concentrated in the nuclei. Initial fluorescence intensity of doxorubicin was 27.3 times that of Lipodox (p
Databáze: OpenAIRE