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Alteration of Runt-related Transcription Factor 3 Gene Expression and Biologic Behavior of Esophageal Carcinoma TE-1 Cells after 5-Azacytidine Intervention

  • Wang, Shuai (Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University) ;
  • Liu, Hong (Department of Otorhinolaryngology, Provincial Hospital Affiliated to Shandong University) ;
  • Akhtar, Javed (Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University) ;
  • Chen, Hua-Xia (Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University) ;
  • Wang, Zhou (Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University)
  • Published : 2013.09.30

Abstract

5-Azacytidine (5-azaC) was originally identified as an anticancer drug (NSC102876) which can cause hypomethylation of tumor suppressor genes. To assess its effects on runt-related transcription factor 3 (RUNX3), expression levels and the promoter methylation status of the RUNX3 gene were assessed. We also investigated alteration of biologic behavior of esophageal carcinoma TE-1 cells. MTT assays showed 5-azaC inhibited the proliferation of TE-1 cells in a time and dose-dependent way. Although other genes could be demethylated after 5-azaC intervention, we focused on RUNX3 gene in this study. The expression level of RUNX3 mRNA increased significantly in TE-1 cells after treatment with 5-azaC at hypotoxic levels. RT-PCR showed 5-azaC at $50{\mu}M$ had the highest RUNX3-induction activity. Methylation-specific PCR indicated that 5-azaC induced RUNX3 expression through demethylation. Migration and invasion of TE-1 cells were inhibited by 5-azaC, along with growth of Eca109 xenografts in nude mice. In conclusion, we demonstrate that the RUNX3 gene can be reactivated by the demethylation reagent 5-azaC, which inhibits the proliferation, migration and invasion of esophageal carcinoma TE-1 cells.

Keywords

5-azacytidine;RUNX3 gene;demethylation;biologic behavior;esophageal carcinoma

Acknowledgement

Supported by : Natural Science Foundation of China

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