title: 5-Azacytidine suppresses EC9706 cell proliferation and metastasis by upregulating the expression of SOX17 and CDH1.
abstract: 5-Azacytidine is a well-known anticancer drug that is clinically used in the treatment of breast cancer, melanoma and colon cancer. It has been reported that 5-azacytidine suppresses the biological behavior of esophageal cancer cells. However, corresponding mechanisms remain unclear. In this study, using Transwell invasion and cell proliferation assays, we demonstrated that 5-azacytidine significantly inhibited the metastasis and proliferation of EC9706 cells, and upregulated the expression of cadherin 1 (CDH1) and SRY-box containing gene 17 (SOX17). Moreover, the inhibition of the metastasis of the 5-azacytidine-treated EC9706 cells was impaired following transfection with siRNA targeting CDH1 (CDH1 siRNA), and the inhibition of cell proliferation was attenuated following the downregulation of SOX17 by siRNA targeting SOX17 (SOX17 siRNA). Furthermore, 5-azacytidine remarkably reduced the CDH1 and SOX17 promoter methylation levels, suggesting that 5-azacytidine upregulates the expression of SOX17 and CDH1 by inhibiting the methylation of the SOX17 and CDH1 promoter. The findings of our study confirm that 5-azacytidine suppresses the proliferation and metastasis of EC9706 esophageal cancer cells by upregulating the expression of CDH1 and SOX17. The expression levels of CDH1 and SOX17 negatively correlate with the promoter methylation levels. CDH1 and SOX17 are potential indicators of the clinical application of 5-azacytidine.
authors: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Wenli
authors: W
authors: Li
authors: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266011, P.R. China.
authors: Dan
authors: D
authors: Wu
authors: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266011, P.R. China.
authors: Ziyu
authors: Z
authors: Niu
authors: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266011, P.R. China.
authors: Dalei
authors: D
authors: Jiang
authors: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266011, P.R. China.
authors: Huan
authors: H
authors: Ma
authors: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266011, P.R. China.
authors: Heming
authors: H
authors: He
authors: Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Xiuli
authors: X
authors: Zuo
authors: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266011, P.R. China.
authors: Xiangjun
authors: X
authors: Xie
authors: Department of Gastroenterology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266011, P.R. China.
authors: Yuanlong
authors: Y
authors: He
mesh_terms: D015703:Antigens, CD; D001374:Azacitidine / Q000494:pharmacology*; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic / Q000235:genetics; D055760:SOXF Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C109188:SOX17 protein, human; D055760:SOXF Transcription Factors; D001374:Azacitidine