Androgen receptor decreases the cytotoxic effects of chemotherapeutic drugs in upper urinary tract urothelial carcinoma cells

Hsieh,Teng-Fu; Chen,Chi-Cheng; Yu,Ai-Lin; Ma,Wen-Lung; Zhang,Caixia; Shyr,Chih-Rong; Chang,Chawnshang

doi:10.3892/ol.2013.1140

Androgen receptor decreases the cytotoxic effects of chemotherapeutic drugs in upper urinary tract urothelial carcinoma cells

Authors:
- Teng-Fu Hsieh
- Chi-Cheng Chen
- Ai-Lin Yu
- Wen-Lung Ma
- Caixia Zhang
- Chih-Rong Shyr
- Chawnshang Chang
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Affiliations: Division of Urology, Department of Surgery, Buddhist Tzu Chi General Hospital, Taichung Branch, Taichung 40427, Taiwan, R.O.C., Sex Hormone Research Center, China Medical University/Hospital, Taichung 40454, Taiwan, R.O.C., George Whipple Lab for Cancer Research, Departments of Pathology, Urology and Radiation Oncology and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA
Published online on: January 18, 2013 https://doi.org/10.3892/ol.2013.1140
Pages: 1325-1330

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Abstract

Upper urinary tract urothelial carcinomas (UUTUCs) represent relatively uncommon yet devastating tumors that affect more males than females. However, the correlation between gender difference and disease progression remains unclear. Androgen and the androgen receptor (AR) were previously hypothesized to account for the gender difference in the incidence of urothelial carcinomas; however, the role of AR in the development and progression of UUTUCs is not well understood. In addition, although UUTUCs are responsive to chemotherapy, various responses are presented among patients. Therefore, the aim of the present study was to determine the role of AR in the response of UUTUC cells to chemotherapeutic drugs. In this study, AR overexpression in UUTUC cells (BFTC 909) was identified to reduce the cytotoxic effect of chemotherapeutic drugs, including doxorubicin, cisplatin and mitomycin C and protected cells from drug‑induced death. The expression of ABCG2, an ATP‑binding cassette half‑transporter associated with multidrug resistance, was increased in AR‑overexpressing BFTC cells. In addition, use of the AR degradation enhancer, ASC‑J9®, repressed the AR effect on increasing cell viability under drug treatment. In summary, results of the present study indicate that the status of AR expression levels in UUTUCs may be a significant factor in affecting the efficacy of chemotherapy and classic chemotherapeutic drugs and AR targeted therapy may provide a novel potential therapeutic approach to improve treatment of UUTUCs.

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