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

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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.

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This study was supported by Science and Technology Planning Project of Guangdong Province, China (2009B030801317), Medical Scientific Research Foundation of Guangdong Province, China (B2011229), and Youth Foundation of Cancer Hospital of Shantou University Medical College, China [(2009) 5].

Ethical standard

This study was approved by the medical ethics committee of Cancer Hospital of Shantou University Medical College. And written informed consent was obtained from all the patients.

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The authors declare that they have no conflict of interest.

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Correspondence to Xiao Wu.

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Xiao Wu and Yi-xuan Zhuang have contributed equally to this work.

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Wu, X., Zhuang, Yx., Hong, Cq. et al. Clinical importance and therapeutic implication of E-cadherin gene methylation in human ovarian cancer. Med Oncol 31, 100 (2014).

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