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 |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Urology Pharmacology lcsh:RC870-923 doxorubicin Flow cytometry 03 medical and health sciences 0302 clinical medicine Fluorescence microscope endocytosis Medicine Distribution (pharmacology) Doxorubicin Cytotoxicity Survival rate IC50 Bladder cancer medicine.diagnostic_test business.industry lipo-doxorubicin lcsh:Diseases of the genitourinary system. Urology medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis bladder cancer business medicine.drug |
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 |
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