Research Papers:

Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer

Zhiqun Shang, Yanjun Li, Iawen Hsu, Minghao Zhang, Jing Tian, Simeng Wen, Ruifa Han, Edward M. Messing, Chawnshang Chang, Yuanjie Niu and Shuyuan Yeh _

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Oncotarget. 2016; 7:27325-27335. https://doi.org/10.18632/oncotarget.8756

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Zhiqun Shang1,2,Yanjun Li1, Iawen Hsu2, Minghao Zhang1, Jing Tian1,2, Simeng Wen1,2,*, Ruifa Han1, Edward M. Messing2,*, Chawnshang Chang1,2, Yuanjie Niu1,2 and Shuyuan Yeh1,2

1 Chawnshang Chang Sex Hormone Research Center, Tianjin Institute of Urology, The 2nd Hospital of Tianjin Medical University, Tianjin, China

2 George Whipple Lab for Cancer Research, Departments of Urology, Pathology and the Cancer Center, University of Rochester, Rochester, New York, United States of America

* co-authors

Correspondence to:

Yuanjie Niu, email:

Shuyuan Yeh, email:

Keywords: Bacillus Calmette-Guérin, bladder cancer, estrogen, estrogen receptor alpha

Received: October 11, 2015 Accepted: January 24, 2016 Published: April 15, 2016


Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence.

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