Transcriptional regulation of E-cadherin and oncoprotein E۷ by valproic acid in HPV positive cell lines

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, TC۱, MKN۴۵, and HCT۱۱۶ cell lines.  This study assesses the effects of VPA on human papillomavirus E۷ expression in HPV positive cell lines. Materials and Methods: Cell lines were treated by۲ mmol/l VPA and expression of E-cadherin and E۷ 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 ۱.۸ times in HCT۱۱۶ and MKN۴۵ cell lines, also the mean of E-cadherin mRNA levels is up-regulated ۲.۹ times in HeLa and TC۱ cell lines. So, E-cadherin augmentation induced by VPA in HeLa and TC-۱, HPV positive cell lines, is higher than HPV negative cell lines MKN۴۵ and HCT۱۱۶. The mean of HPV E۷ expression is decreased by VPA, ۴.۶ times in in HeLa and TC-۱ 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 E۷ reduces the expression of E-cadherin, reduction of HPV E۷ 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.

Keywords:

Cervical Cancer , E-cadherin , HPV , Valproic acid