Transcriptional regulation of E-cadherin and oncoprotein E7 by valproic acid in HPV positive cell lines

Document Type: Original Article


1 Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran

3 Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran


Objective(s): Valproic acid (VPA) has proven to be as one of the most promising useful drug with anticancer properties.In this study, we investigate the VPA effects on E-cadherin expression in HeLa, TC1, MKN45, and HCT116 cell lines.  This study assesses the effects of VPA on human papillomavirus E7 expression in HPV positive cell lines.
Materials and Methods: Cell lines were treated by2 mmol/l VPA and expression of E-cadherin and E7 was analyzed by quantitative real-time PCR. Student’s t test and ANOVA were used to determine changes in expression levels.
Results:The results revealed that mean of E-cadherin expression is increased by VPA 1.8 times in HCT116 and MKN45 cell lines, also the mean of E-cadherin mRNA levels is up-regulated 2.9 times in HeLa and TC1 cell lines. So, E-cadherin augmentation induced by VPA in HeLa and TC-1, HPV positive cell lines, is higher than HPV negative cell lines MKN45 and HCT116. The mean of HPV E7 expression is decreased by VPA, 4.6 times in in HeLa and TC-1 cell lines. 
Conclusion: This study demonstrates that re-expression of E-cadherin by VPA in HPV positive cell lines is more than HPV negative cell lines. Whereas, HPV E7 reduces the expression of E-cadherin, reduction of HPV E7 expression by VPA is related to more augmentation of E-cadherin in HPV positive cell lines. So, this study demonstrates that VPA has more anticancer properties in HPV positive cell lines, and could potentially be a promising candidate for cervical cancer treatment.


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