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Updated: Jun 27, 2026
Multiplexed Live-Cell Imaging for Drug Responses in Patient-Derived Organoid Models of Cancer
Published on: January 5, 2024
Grade-dependent effects on cell cycle progression and apoptosis in response to doxorubicin in human bladder cancer
Dimitrios J Stravopodis1, Panagiotis K Karkoulis, Eumorphia G Konstantakou
1Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Zografou, 15784 Athens, Greece.
Abstract:
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.
Insights
Doxorubicin triggers cell cycle arrest and apoptosis in bladder cancer cells. Gene expression patterns may predict cancer grade and treatment response to this chemotherapy agent.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Doxorubicin is a key chemotherapy drug for muscle-invasive urinary bladder cancer.
- It functions as a topoisomerase II poison, disrupting cancer cell progression and inducing death.
Purpose of the Study:
- To investigate doxorubicin's effects on cell cycle and apoptosis in bladder cancer.
- To identify potential gene biomarkers for predicting prognosis and treatment response.
Main Methods:
- Flow cytometry (FACS) analysis.
- Western immunoblotting.
- Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).
Main Results:
- Doxorubicin induced dose-dependent cell cycle arrest (G2/M and/or G1/S).
- Observed apoptosis markers included reduced FasL, activated Caspases (8, 9, 3), cleaved PARP, Lamin A/C, Bcl-XL/S, and Hsp90.
- Specific gene expression patterns were associated with differentiation grade and doxorubicin response.
Conclusions:
- Doxorubicin effectively induces cell death in bladder cancer through cell cycle arrest and apoptosis.
- Gene expression profiles of Cyclin-E2, Cyclin-F, p63, p73, FasL, TRAIL, Tweak, Tweak-R, XAF-1, OPG, and Bok may indicate differentiation grade.
- Genes like Cyclin-B2, GADD45A, p73, FasL, Bik, Bim, TRAIL, Fas, Tweak-R, XAF-1, Bcl-2, Survivin, OPG, DcR2, and Bcl-XL could serve as biomarkers for doxorubicin response.
