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KMID : 1034820160120040345
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Molecular & Cellular Toxicology
2016 Volume.12 No. 4 p.345 ~ p.357
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Identification of aberrant DNA methylation involved in chemoradiation-resistant HCT116 cells via methylation-specific microarray
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Xiong Wei
Li Yun-Feng
Liu Shan
Chen Ting
Zhang Hong-Tao
Yang Zhi-Bin
Ding Ying-Ying
Gao De-Pei
Wang Guan-Shun
Dong Jian
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Abstract
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Preoperative 5-fluorouracil (5-FU) based chemoradiation is regarded as the standard treatment for locally advanced colorectal cancer (CRC). However, advances in using 5-FU in chemoradiotherapy treatment of CRC are limited by the resistant to the chemoradiotherapy. It has been demonstrated that aberrant methylation contributes to radioresistance in a human colorectal tumor cell line. So we analyzed the differential DNA methylation patterns by methylationspecific microarray in a 5-FU-based concurrent chemoradiotherapy resistance cell model which was established by using human CRC cell line HCT116. As a result, we detected a total of 3719 hypomethylated sites and 27940 hypermethylated sites in CRR cells compared to the control. Furthermore, we analyzed top 10 GO terms involved in significantly differential DNA methylation patterns resulted from the 5-FU-based CRR through GO analyses. To further explore the molecular basis of 5-FU-based CRR in CRC cells, CYP1B1 and CYP2C9 genes expression level were shown down regulated by qRT-PCR. These findings might provide a novel insight for chemoradiation resistance in CRC and provide a potential therapy method in CRC patients.
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KEYWORD
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DNA methylation, Chemoradiation-resistant, Colorectal cancer, HCT116 cells
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