title: Decitabine inhibits the cell growth of cholangiocarcinoma in cultured cell lines and mouse xenografts.
abstract: Decitabine (DAC), an inhibitor of DNA methyltransferase, demonstrates antitumor activities in various types of cancer. However, its therapeutic potential for cholangiocarcinoma (CCA), one of the most aggressive gastrointestinal malignancies, remains to be explored. The present study investigated the antiproliferative effects of DAC on CCA cellsin vitroandin vivo. Human CCA cell lines, TFK-1 and QBC939, were used as models to investigate DAC on the cell growth and proliferation of CCA. Cell proliferation was evaluated by Cell Counting Kit-8 assay combined with clonogenic survival assay. Flow cytometry, Hoechst 33342/propidium iodide staining and green fluorescent protein-tagged MAP-LC3 detection were applied to determine cell cycle progression, apoptosis and autophagy. Nude mice with TFK-1 xenografts were evaluated for tumor growth following DAC treatment. DAC was observed to significantly suppress the proliferation of cultured TFK-1 and QBC939 cells, accompanied with enhanced apoptosis, autophagy and cell cycle arrest at G2/M phase. In TFK-1 mouse xenografts, DAC retarded the tumor growth and increased the survival of CCA tumor-bearing mice.
authors.affiliation: Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Shunchang
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Shengquan
authors.initials: S
authors.lastname: Zou
keywords: apoptosis; autophagy; cell cycle; cholangiocarcinoma; decitabine