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The effect of celecoxib on DNA methylation of CDH13, TFPI2, and FSTL1 in squamous cell carcinoma of the esophagus in vivo.
- Source :
-
Anti-cancer drugs [Anticancer Drugs] 2016 Oct; Vol. 27 (9), pp. 848-53. - Publication Year :
- 2016
-
Abstract
- This study examined the in-vivo effect of the NSAID celecoxib on DNA methylation in the promoter region of the tumor-suppressor genes cadherin 13, tissue factor pathway inhibitor 12, and follistatin-like protein 1, and on apoptosis, in esophageal squamous cell carcinoma (ESCC). Forty-five patients who underwent an esophagectomy for ESCC were allocated to either a treatment group (n=22) or a control group (n=23). Patients in the treatment group were administered 800 mg/day of celecoxib for 14 days before surgery. Patients in the control group did not take any type of NSAID. Biopsies of the tumor were collected before surgery and tissue from the resection specimens after surgery. Methylation-specific PCR was used to measure DNA methylation and apoptosis was measured by flow cytometry. There was no difference in the proportion of patients with methylation for each of the genes between the patient groups before treatment. In those patients with pretreatment methylation, there was a significant reduction in the proportion with methylation and a significant increase in the corresponding messenger RNA expression after treatment with celecoxib. In those tissues in which there was a reduction in methylation following celecoxib treatment, there was a significant increase in the percentage of apoptotic cells, but not in the tissues with no change in methylation. In ESCC, in-vivo treatment with celecoxib is associated with a reduction in DNA methylation and increase in messenger RNA expression of tumor-suppressor genes, and increases in apoptosis.
- Subjects :
- Adult
Aged
Carcinoma, Squamous Cell genetics
Carcinoma, Squamous Cell surgery
Cyclooxygenase 2 Inhibitors administration & dosage
Esophageal Neoplasms genetics
Esophageal Neoplasms surgery
Female
Gene Expression drug effects
Genes, Tumor Suppressor drug effects
Humans
Male
Middle Aged
Promoter Regions, Genetic drug effects
Cadherins genetics
Carcinoma, Squamous Cell drug therapy
Celecoxib administration & dosage
DNA Methylation drug effects
Esophageal Neoplasms drug therapy
Follistatin-Related Proteins genetics
Glycoproteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5741
- Volume :
- 27
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Anti-cancer drugs
- Publication Type :
- Academic Journal
- Accession number :
- 27400374
- Full Text :
- https://doi.org/10.1097/CAD.0000000000000396