Περίληψη:
Doxorubicin is an important component of combination therapy for muscle-invasive urinary bladder cancer. Treatment with this topoisomerase II poison is able to interfere with cell cycle progression and lead to cancer cell death. Using FACS analysis, Western immunoblotting and semi-quantitative RT-PCR, we studied the effects of doxorubicin on cell cycle progression and apoptosis, and also explored the possibility of using groups of genes as biomarkers of prognosis and/ or response to doxorubicin treatment in human urinary bladder cancer cells. Doxorubicin induced dose-dependent G2/M and/or G1/S cell cycle arrest, followed by grade- and dose-dependent reduction in the amount of the cytosolic trimeric form of FasL, activation of Caspase-8, Caspase-9, Caspase-3, cleavage of PARP, Lamin A/C, Bcl-XL/S and interestingly Hsp90, and finally cell death. Data presented here also suggest the use of the expression patterns of Cyclin-E2, Cyclin-F, p63, p73, FasL, TRAIL, Tweak, Tweak-R, XAF-1, OPG and Bok genes for identification of the differentiation grade, and Cyclin-B2, GADD45A, p73, FasL, Bik, Bim, TRAIL, Fas, Tweak-R, XAF-1, Bcl-2, Survivin, OPG, DcR2 and Bcl-XL genes for the detection of response to doxorubicin in human bladder cancer cells.
Συγγραφείς:
Stravopodis, D.J.
Karkoulis, P.K.
Konstantakou, E.G.
Melachroinou, S.
Lampidonis, A.D.
Anastasiou, D.
Kachrilas, S.
Messini-Nikolaki, N.
Papassideri, I.S.
Aravantinos, G.
Margaritis, L.H.
Voutsinos, G.E.
Λέξεις-κλειδιά:
BIK protein; BIM protein; caspase 3; caspase 8; caspase 9; cyclin B2; cyclin E; cytokine; cytokine receptor; decoy receptor 2; doxorubicin; Fas antigen; Fas ligand; growth arrest and DNA damage inducible protein 45; heat shock protein 90; lamin A; lamin C; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; osteoprotegerin; paclitaxel; protein bcl 2; protein bcl 2 related ovarian killer; protein bcl xl; protein p63; protein p73; survivin; tumor necrosis factor related apoptosis inducing ligand; tumor necrosis factor related weak inducer of apoptosis protein; unclassified drug; X linked inhibitor of apoptosis associated factor 1; antineoplastic antibiotic; cell cycle protein; messenger RNA; tumor marker, apoptosis; article; bladder cancer; cancer cell culture; cancer grading; cell cycle arrest; cell cycle G1 phase; cell cycle G2 phase; cell cycle M phase; cell cycle progression; cell cycle S phase; cell death; controlled study; enzyme activation; fluorescence activated cell sorting; human; human cell; priority journal; prognosis; protein expression; reverse transcription polymerase chain reaction; treatment outcome; Western blotting; apoptosis; bladder tumor; cancer staging; cell cycle; cell differentiation; cell proliferation; DNA microarray; drug effect; flow cytometry; gene expression profiling; genetics; immunoblotting; metabolism; pathology; transitional cell carcinoma; tumor cell line, Antibiotics, Antineoplastic; Apoptosis; Blotting, Western; Carcinoma, Transitional Cell; Cell Cycle; Cell Cycle Proteins; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Doxorubicin; Flow Cytometry; Gene Expression Profiling; Humans; Immunoblotting; Neoplasm Staging; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Markers, Biological; Urinary Bladder Neoplasms
