机构：[1]Department of Cardiothoracic Surgery, Beijing Friendship Hospital[2]Beijing Xuanwu Hospital, Capital Medical University, Beijing, P.R. China首都医科大学宣武医院[3]Thoracic Oncology Laboratory, Department of Surgery, UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0128, USA[4]Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan, R.O.C.
Secreted Wingless type (Wnt) ligands have previously been shown to be involved in tumor developmental processes and oncogenesis. Aberrant promoter methylation of Writ inhibitory factor-1 (WIF-1) is a fundamental mechanism of epigenetic silencing in human cancers. Procaine, a local anesthetic drug, and procainamide, a drug for the treatment of cardiac arrhythmias, have been reported as inhibitors of DNA methylation, causing demethylation and reactivation of methylation-silenced genes such as RAR beta and GSTP1. The promoter demethylation of WIF-1 has not previously been reported on. We demonstrated Previously that WIF-1 is silenced due to promoter hypermethylation in lung cancer cell lines. In this study, we demonstrate promoter demethylation of WIF-1; restoration of WIF-1 expression, and underexpression of cytosolic beta-catenin protein and TCF reporter activity, after procaine and procainamide treatment in H460 and A549 cell lines. Our results provide the first evidence that procaine and procainamide reactivate WIF-1 in these cancer cells and downregulate the Writ canonical pathway. These results further suggest that procaine and procainamide may have a potential use for preventing the development Of lung cancer.
基金：
NIH grant RO1 CA 093708-01A3, and the Larry Hall memorial trust and Bonnie J. and Anthony Addario; the Bonnie J. Addario Lung Cancer Foundation;
the Eileen D. Ludwig Endowed for Thoracic Oncology Research, Kazan, McClain, Abrams, Fernandez, Lyons, Greenwood, Harley & Oberman Foundation, Inc.;
Estate of Robert Griffiths; Estate of Norman Mancini; the Barbara Isackson Lung Cancer Research Fund.
第一作者机构：[1]Department of Cardiothoracic Surgery, Beijing Friendship Hospital[3]Thoracic Oncology Laboratory, Department of Surgery, UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0128, USA
通讯作者：
通讯机构：[*]Department of Surgery, University of California, San Francisco, Box 0128, San Francisco, CA 94143-0128, USA
推荐引用方式(GB/T 7714)：
ZHI GAO,ZHIDONG XU,MING-SZU HUNG,et al.Procaine and procainamide inhibit the Wnt canonical pathway by promoter demethylation of WIF-1 in lung cancer cells[J].ONCOLOGY REPORTS.2009,22(6):1479-1484.doi:10.3892/or_00000590.
APA：
ZHI GAO,ZHIDONG XU,MING-SZU HUNG,YU-CHING LIN,TIANYOU WANG...&LIANG YOU.(2009).Procaine and procainamide inhibit the Wnt canonical pathway by promoter demethylation of WIF-1 in lung cancer cells.ONCOLOGY REPORTS,22,(6)
MLA：
ZHI GAO,et al."Procaine and procainamide inhibit the Wnt canonical pathway by promoter demethylation of WIF-1 in lung cancer cells".ONCOLOGY REPORTS 22..6(2009):1479-1484
