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

来源 :2014医学科学前沿暨第三届个体化治疗与抗肿瘤药物研究新趋向研讨会 | 被引量 : 0次 | 上传用户:ZHANGLONGQI008
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  Background: E-cadherin is widely expressed in epithelial cells and acts as a pivotal tumor suppressor.The promoter methylation of E-cadherin has been reported to closely relate to its downregulation in many kinds of cancers.Methods: E-cadherin expression and methylation status were detected by Immunohistochemistry (IHC) and Methylation-specific PCR (MS-PCR) in 50 ovarian cancer tissues.5-Aza-2-deoxycytidine was used to demethylate E-cadherin 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.Results: Down regulation of E-cadherin expression was observed in 60% of ovarian cancer tissues (30/50) by IHC, whereas MS-PCR result indicated that E-cadherin was methylated in 64% of (32/50) ovarian cancer specimens.And E-cadherin expression was significantly correlated with E-cadherin methylation (P=0.004).5-Aza-2-deoxycytidine was used to process SKOV3 and ES2 ovarian cancer cell lines.By MTT experiment, we found that the proliferation of 5-Aza-2-deoxycytidine treated SKOV3 and ES2 were significantly suppressed by 28.0% (P<0.05) and 32.3%(P<0.05).By transwell experiment, the motility of SKOV3 and ES2 were found to be significantly suppressed by 38.2% and 27.4% (P<0.05) respectively after treated with 5-Aza-2-deoxycytidine.Conclusions: E-cadherin methylation is one of the main reasons for the expression reduction in ovarian cancer.5-Aza-2-deoxycytidine treatment could significantly restore the expression of E-cadherin and suppress growth and invasion of SKOV3 and ES2 cells.These results suggest E-cadherin methylation may be a promising target for ovarian cancer therapy.
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