Clinical importance and therapeutic implication of E-cadherin gene methylation in human ovarian cancer

Abstract

E-cadherin (E-cad) is widely expressed in epithelial cells and acts as a pivotal tumor suppressor. The promoter methylation of E-cad has been reported to closely relate to its downregulation in many kinds of cancers. E-cad expression and methylation status were detected by immunohistochemistry (IHC) and methylation-specific polymerase chain reaction (MS-PCR) in 50 ovarian cancer tissues. 5-Aza-2'-deoxycytidine (5-Aza-dC) was used to demethylate E-cad in SKOV3 and ES2 ovarian cancer cell lines, of which the effect was verified by Western blot and MS-PCR. Then MTT and transwell experiments were conducted to detect the capacity of cell proliferation and migration for these cells. Downregulation of E-cad expression was observed in 60 % of ovarian cancer tissues (30/50) by IHC, whereas MS-PCR result indicated that E-cad was methylated in 64 % of (32/50) ovarian cancer specimens. And E-cad expression was significantly correlated with E-cad methylation (P = 0.004). 5-Aza-dC was used to process SKOV3 and ES2 ovarian cancer cell lines. By MTT experiment, we found that the proliferation of 5-Aza-dC-treated SKOV3 and ES2 was significantly suppressed by 28.0 % (P < 0.05) and 32.3 % (P < 0.05). By transwell experiment, the motility of SKOV3 and ES2 was found to be significantly suppressed by 38.2 and 27.4 % (P < 0.05), respectively, after treated with 5-Aza-dC. E-cad methylation is one of the main reasons for the expression reduction in ovarian cancer. 5-Aza-dC treatment could significantly restore the expression of E-cad and suppress growth and invasion of SKOV3 and ES2 cells. These results suggest E-cad methylation may be a promising target for ovarian cancer therapy.