Valproic Acid (VPA) inhibits the epithelial-mesenchymal transition in prostate carcinoma via the dual suppression of SMAD4

10^th Global Annual Oncologists Meeting

July 11-13, 2016 Cologne, Germany

Qinghua Xia, Xiaopeng Lan, Guoliang Lu, Chuanwei Yuan, Shaowei Mao, Wei Jiang, Yougen Chen and Xunbo Jin

Provincial Hospital, China
Dongying People`s Hospital, China

Posters & Accepted Abstracts: J Cancer Sci Ther

Abstract :

The epithelial-mesenchymal transition (EMT) plays an important role in cancer metastasis. Previous studies have reported that Valproic Acid (VPA) suppresses prostate carcinoma (PCa) cell metastasis and down-regulates SMAD4 protein levels, which is the key molecule in TGF-�²-induced EMT. However, the correlation between VPA and the EMT in PCa remains uncertain. Markers of the EMT in PCa cells and xenografts were molecularly assessed after VPA treatment. The expression and mono-ubiquitination of SMAD4 were also analyzed. After transfection with plasmids that express SMAD4 or short hairpin RNA (shRNA) for SMAD4 down-regulation, markers of EMT were examined to confirm whether VPA inhibits the EMT of PCa cells through the suppression of SMAD4. VPA induced the increase in E-cadherin (p<0.05), and the decrease in N-cadherin (p<0.05) and Vimentin (p<0.05), in PCa cells and xenografts. SMAD4 mRNA and protein levels were repressed by VPA (p<0.05), whereas the level of mono-ubiquitinated SMAD4 was increased (p<0.05). SMAD4 knockdown significantly increased E-cadherin expression in PC3 cells, but SMAD4 overexpression abolished the VPA-mediated EMT-inhibitory effect. VPA inhibits the EMT in PCa cells via the inhibition of SMAD4 expression and the mono-ubiquitination of SMAD4. VPA could serve as a promising agent in PCa treatment, with new strategies based on its diverse effects on post-transcriptional regulation.

Biography :

Email: xqhgege@hotmail.com