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Status |
Public on Nov 30, 2016 |
Title |
Enzalutamide inhibits proliferation of gemcitabine-resistant bladder cancer cells with increased androgen receptor expression |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance to these chemotherapeutic agents. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In the present study, we showed the expression and role of AR in gemcitabine-resistant bladder cancer cells and examined the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling and network analysis, which revealed increased AR expression and AR-related gene network in T24GR cells. Quantitative RT-PCR and Western blot analysis confirmed increased expression of AR in T24GR cells compared with parental T24 cells, which was associated with more potent transcriptional activity of AR in T24GR cells. The number of AR gene copy in T24GR cells was twice as many as that of T24 cells. Knockdown of AR expression by siRNA resulted in inhibition of proliferation of T24GR cells. Cell culture in charcoal-stripped serum and treatment with enzalutamide also inhibited growth of T24GR cells, which was accompanied by cell cycle arrest. Lastly, the AR transcriptional activity was found to be reduced in T24GR cells by enzalutamide treatment. Our results suggest that blockade of AR signaling by enzalutamide might be effective for patients with advanced gemcitabine-resistant bladder cancer with increased AR expression.
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Overall design |
T24 human bladder cancer cell line was obtained from RIKEN Cell Bank (Tsukuba, Japan).
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Contributor(s) |
Kojima T, Kameyama K, Kato T, Fujita Y, Kawakami K, Mizutani K, Deguchi T, Ito M |
Citation missing |
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Submission date |
Feb 12, 2016 |
Last update date |
Apr 23, 2018 |
Contact name |
Toshio Kojima |
Organization name |
Toyohashi University of Technology
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Department |
Health Care Center
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Street address |
1-1 Hibarigaoka Tenpaku-cho
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City |
Toyohashi |
ZIP/Postal code |
441-8580 |
Country |
Japan |
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Platforms (1) |
GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
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Samples (6)
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Relations |
BioProject |
PRJNA311949 |