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地西他滨抑制培养细胞系和小鼠异种移植瘤中胆管癌的细胞生长。

Decitabine inhibits the cell growth of cholangiocarcinoma in cultured cell lines and mouse xenografts.

作者信息

Wang Bing, Li Hongbo, Yang Rui, Zhou Shunchang, Zou Shengquan

机构信息

Department of General Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.

出版信息

Oncol Lett. 2014 Nov;8(5):1919-1924. doi: 10.3892/ol.2014.2499. Epub 2014 Sep 4.

DOI:10.3892/ol.2014.2499
PMID:25295073
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4186605/
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 cells and . 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.

摘要

地西他滨（DAC）是一种DNA甲基转移酶抑制剂，在多种癌症类型中都表现出抗肿瘤活性。然而，其对胆管癌（CCA）这种最具侵袭性的胃肠道恶性肿瘤之一的治疗潜力仍有待探索。本研究调查了DAC对CCA细胞的抗增殖作用。人CCA细胞系TFK-1和QBC939被用作模型来研究DAC对CCA细胞生长和增殖的影响。通过细胞计数试剂盒-8检测结合克隆形成存活检测来评估细胞增殖。应用流式细胞术、Hoechst 33342/碘化丙啶染色和绿色荧光蛋白标记的MAP-LC3检测来确定细胞周期进程、细胞凋亡和自噬。对携带TFK-1异种移植瘤的裸鼠在接受DAC治疗后评估肿瘤生长情况。观察到DAC能显著抑制培养的TFK-1和QBC939细胞的增殖，同时伴有细胞凋亡增加、自噬增强以及细胞周期阻滞于G2/M期。在TFK-1小鼠异种移植瘤模型中，DAC延缓了肿瘤生长并提高了荷CCA肿瘤小鼠的存活率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/051f/4186605/9b8b4f892ec7/OL-08-05-1919-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/051f/4186605/71ff75ebfd33/OL-08-05-1919-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/051f/4186605/2aa2ae8b9633/OL-08-05-1919-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/051f/4186605/c0aa98107f2c/OL-08-05-1919-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/051f/4186605/bc9e0d13afe4/OL-08-05-1919-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/051f/4186605/9b8b4f892ec7/OL-08-05-1919-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/051f/4186605/71ff75ebfd33/OL-08-05-1919-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/051f/4186605/2aa2ae8b9633/OL-08-05-1919-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/051f/4186605/c0aa98107f2c/OL-08-05-1919-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/051f/4186605/bc9e0d13afe4/OL-08-05-1919-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/051f/4186605/9b8b4f892ec7/OL-08-05-1919-g04.jpg

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