Abstract: Objective: To evaluate the effect of the DNA methyltransferase (DNMT) inhibitor 5 - aza -2 '- deoxycytidine (5-Aza-CdR) combined histone acetylation Enzymes (HDAC) inhibitor Sodium 4-Phenylbutyrate (SPB) on the expression of epithelial cadherin (E-cad) expression of nude mice models with ovarian cancer cell lineSKOV3. Methods: 40 nude mice were implanted ovarian cancer cell lineSKOV3 into abdominal cavity as animal model. The models were randomly divided into four groups. Controlled group was injected phosphate-buffered saline into abdominal cavity, 5-Aza-CdR and SPB were used respectively in other two groups, and 5-Aza-CdR plus SPB were used in the fourth group. After two weeks of injection, the expressions of DNMT1, HDAC1 and E-cad in the ovarian cancer xenograft tumors by immunohistochemical staining. The CpG island methylation status of E-cadherin promoter region in xenograft tumors were analyzed by methylation specific PCR (MSP). The mRNA and the protein expressions of E-cad were also compared among the four groups. Results: DNMT1 and HDAC1 were highly expressed in xenograft tumors. 5-Aza-CdR can inhibit the expression of DNMT1 and SPB can inhibit the expression of HDAC1 which were indicated by comparison with controlled group (P <0.05). The combining 5-Aza-CdR with SPB have no obvious synergistic effect on the inhibition of DNMT1 and HDAC1. 5-Aza-CdR can induce methylated E-cad gene demethylation which made E-cad mRNA and protein expressions recovered or even better. 5-Aza-CdR combined with SPB can induce methylated E-cad gene demethylation and recover the E-cad mRNA and protein expressions compared with other groups. Conclusion: 5-Aza-CdR can reduce the E-cad gene promoter methylation and make E-cad mRNA and protein expressions recovered. 5-Aza-CdR combined with SPB can accomplish synergetic effect and enhance the expression of methylated E-cad gene significantly which played an important role in the treatment of ovarian cancer

Key words: Ovarian cancer, E-cadherin, 5-Aza-2'-deoxycytidine, Sodium 4-Phenylbutyrate , Demethylation