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

Abstract：

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Wu M,Sheng L,Cheng M,Zhang H,Jiang Y,Lin S,Liang Y,Zhu F,Liu Z,Zhang Y,Zhang X,Gao Q,Chen D,Li J,Li Y

doi

10.1038/s41388-019-0799-1

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

5425-5439

issue

27

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-019-0799-1

journal_volume

38

pub_type

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