Regulation and expression of aberrant methylation on irinotecan metabolic genes CES2, UGT1A1 and GUSB in the in-vitro cultured colorectal cancer cells.
OBJECTIVE
To evaluate the aberrant methylation gene expression related to the irinotecan (CPT-11) metabolic enzymes in different colorectal cancer cell strains; provide new thoughts and measures for reverse of tumor drug resistance.


METHODS
Studied the aberrant methylation state of CES2, UGT1A1 and GUSB in eight colorectal cancer cell strains through MSP method; and analyze the expression of the target gene after being dealt with DAC.


RESULTS
UGT1A1 showed methylation in five cell strains, while CES2 and GUSB respectively showed consistent unmethylation or hemimethylation. After being dealt with DAC, CES2 and GUSB mRNA showed different expressions but not significant. The expression quantity of UGT1A1mRNA in the low-expression cell strains increased significantly. The expression of UGT1A1 protein where POSITIVE presented low expression was up-regulated to different degrees. Negative tropism was found in CES2 and UGT1A1.


CONCLUSIONS
Methylation in UGT1A1 gene expression silencing as an important mechanism; methylation could provide an effective target for methylation regulation intervening in the treatment of CPT-11. Meanwhile, studies found that the changes in expressions of CES2 and GUSB might be resulted from some unknown target that still existed during the regulation, or from the influence of methylation in the non-core zone of promoters on the gene transcription.
Department of Medicine Oncology, Fuzhou General Hospital of Nanjing Military Command, 350025 Fuzhou, Fujian, China. Electronic address: zjxfw@vip.tom.com.
Fang-Wei
FW
Xie
Department of Medicine Oncology, Fuzhou General Hospital of Nanjing Military Command, 350025 Fuzhou, Fujian, China.
Yong-Hai
YH
Peng
Department of Medicine Oncology, Fuzhou General Hospital of Nanjing Military Command, 350025 Fuzhou, Fujian, China.
Xi
X
Chen
Department of Medicine Oncology, Fuzhou General Hospital of Nanjing Military Command, 350025 Fuzhou, Fujian, China.
Xiong
X
Chen
Department of Medicine Oncology, Fuzhou General Hospital of Nanjing Military Command, 350025 Fuzhou, Fujian, China.
Jie
J
Li
Department of Medicine Oncology, Fuzhou General Hospital of Nanjing Military Command, 350025 Fuzhou, Fujian, China.
Zong-Yang
ZY
Yu
Department of Medicine Oncology, Fuzhou General Hospital of Nanjing Military Command, 350025 Fuzhou, Fujian, China.
Wen-Wu
WW
Wang
Department of Medicine Oncology, Fuzhou General Hospital of Nanjing Military Command, 350025 Fuzhou, Fujian, China. Electronic address: oyxnong@163.com.
Xue-Nong
XN
Ouyang
D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000378:metabolism; D043182:Carboxylesterase / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005966:Glucuronidase / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics; D000099148:UGT1A1 Enzyme
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D043182:Carboxylesterase; D005966:Glucuronidase; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D012333:RNA, Messenger; D000099148:UGT1A1 Enzyme; C517204:CES2 protein, human
Aberrant methylation; CES2; CPT-11; Colorectal cancer cell; GUSB; Gene expression; UGT1A1