We demonstrate that combined treatment with GSK126 and 5-Aza-2’-deoxycytidine to inhibit methyltransferase activity of EZH2 and DNMT3B synergistically block EC cell proliferation and EC tumor progression in both cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. The gene discussed is DNMT3B; the disease is neoplasm.