Low doses of decitabine improve the chemotherapy efficacy against basal-like bladder cancer by targeting cancer stem cells.

Low dose treatment with the DNA methylation inhibitor decitabine has been shown to be applicable for the management of certain types of cancer. However, its antitumor effect and mechanisms are context dependent and its activity has never been systematically studied in bladder cancer treatment. We used mouse models, cultured cell lines and patient-derived xenografts to demonstrate that low dose decitabine treatment remarkably enhanced the effects of cisplatin and gemcitabine on basal-like bladder cancer both in vivo and in vitro. Genetic lineage tracing revealed that the stemness of a bladder cancer stem cell population was inhibited by decitabine treatment in mice. These effects were accompanied by decreases in genome-wide DNA methylation, gene re-expression, and changes in key cellular regulatory pathways such as STAT3 signaling. These results indicate that this DNA-demethylating reagent is a promising therapeutic approach for basal-like bladder cancer treatment.

Oncogene. 2019 Mar 27 [Epub ahead of print]

Mingqing Wu, Lu Sheng, Maosheng Cheng, Haojie Zhang, Yizhou Jiang, Shuibin Lin, Yu Liang, Fengyu Zhu, Zhenqing Liu, Yingyin Zhang, Xiuhong Zhang, Qian Gao, Demeng Chen, Jiong Li, Yang Li

Department of Genetics, School of Life Science, Anhui Medical University, Hefei, Anhui, 230031, China., Department of Urology, Huadong Hospital, Fudan University, Shanghai, 200040, China., Institute for Advanced Study, Shenzhen University, Shenzhen, Guangdong, 518060, China., Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China., Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry and Broad Stem Cell Research Center, UCLA, Los Angeles, CA, 90095, USA., Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China. ., Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, School of Dentistry and Broad Stem Cell Research Center, UCLA, Los Angeles, CA, 90095, USA. ., Department of Genetics, School of Life Science, Anhui Medical University, Hefei, Anhui, 230031, China. .

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