Establishment and characterization of a bladder cancer cell line with enhanced doxorubicin resistance by mevalonate pathway activation
作者： Annemarie Greife , Jitka Tukova , Christine Steinhoff , Simon D. Scott , Wolfgang A. Schulz
DOI: 10.1007/S13277-014-2959-9
关键词: Apoptosis 、 Bladder cancer 、 Biology 、 Efflux 、 Reporter gene 、 Cell culture 、 Pharmacology 、 Doxorubicin 、 Mevalonate pathway 、 Chemotherapy 、 General Medicine
摘要: Resistance to chemotherapy is a major problem in the treatment of urothelial bladder cancer. Several mechanisms have been identified resistance doxorubicin by analysis resistant carcinoma (UC) cell lines, prominently activation drug efflux pumps and diminished apoptosis. We derived new doxorubicin-resistant line from BFTC-905 UC cells, designated BFTC-905-DOXO-II. A doxorubicin-responsive green fluorescent protein (GFP) reporter assay indicated that BFTC-905-DOXO-II was not due increased pump activity, whereas caspase-3/7 indeed diminished. Gene expression microarray revealed changes proapoptotic antiapoptotic genes, but additionally induction mevalonate (cholesterol) biosynthetic pathway. Treatment with simvastatin restored sensitivity parental line. Induction pathway has reported as mechanism chemoresistance other cancers; this first observation Combinations statins doxorubicin-containing regimens may provide therapeutic advantage such cases.
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