title: Methylation of CHFR sensitizes esophageal squamous cell cancer to docetaxel and paclitaxel.
abstract: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. Both genetic and epigenetic changes are involved in esophageal carcinogenesis. CHFR methylation has been found frequently in different cancers and is regarded as a marker of taxane sensitivity. CHFR methylation was found in 0% (0/16) of normal mucosa, 2.9% (1/34) of grade I dysplasia, 0% (0/8) of grade II dysplasia, 12.5% (1/8) of grade III dysplasia and 45% (49/109) of invasive cancer. When treated with docetaxel or paclitaxel, cell viability was lower in CHFR methylated esophageal cancer cells than in unmethylated cells (p<0.05). No difference was found with either cisplatin or VP16 treatment in either group (p>0.05). In CHFR methylated cells, treatment with docetaxel or paclitaxel resulted in almost all cells being suspended in G0/G1 phase of the cell cycle. After 5-AZ treatment, there was an increased fraction of CHFR-methylated cells in S and G2/M phases (p<0.05). In conclusion, CHFR is frequently methylated in ESCC and the expression of CHFR is regulated by promoter region methylation. CHFR methylation is a late stage event in ESCC. Methylation of CHFR sensitized ESCC cells to taxanes. 5-AZ may re-sensitize chemotherapy resistant in refractory tumors by inducing cell cycle phase re-distribution.
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: Tianyang
authors.initials: T
authors.lastname: Yun
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China.|Medical College of NanKai University, Tianjin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Enqiang
authors.initials: E
authors.lastname: Linghu
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, U.S.A.
authors.forename: Malcolm V
authors.initials: MV
authors.lastname: Brock
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
authors.forename: Dongtao
authors.initials: D
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, U.S.A.
authors.forename: James G
authors.initials: JG
authors.lastname: Herman
authors.affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
keywords: 5-aza-2′-deoxycytidine; CHFR; DNA methylation; chemo-sensitivity; docetaxel; esophageal squamous cell cancer; paclitaxel
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