title: Valproic acid (VPA) promotes the epithelial mesenchymal transition of hepatocarcinoma cells via transcriptional and post-transcriptional up regulation of Snail.
abstract: Due to the low cost and favorable safety profile, valproic acid (VPA) has been considered as a potential candidate drug for therapy of various cancers. Our present study revealed that VPA, at the concentration (1mM) which has no effect on cell proliferation, can significantly increase the in vitro migration and invasion of hepatocarcinoma (HCC) HepG2 and Huh7 cells via induction of epithelial mesenchymal transition (EMT). VPA treatment can significantly increase the mRNA and protein expression of Snail, the key transcription factor of EMT. While knockdown of Snail can abolish VPA induced EMT of HCC cells. It suggested that Snail is essential for VPA induced EMT of HCC cells. VPA treatment also increased the phosphorylation of NF-κB p65. BAY 11-7082, the inhibitor of NF-κB, can significantly abolish VPA induced up regulation of Snail mRNA. Furthermore, VPA can increase the protein expression of Snail since 1h treatment via up regulation of half-lives of Snail protein. The increased protein stabilization of Snail can be attributed to VPA induced phosphorylation of Akt and GSK-3β. Collectively, our present study revealed that VPA can promote the EMT of HCC cells via up regulation of Snail through activation of NF-κB and Akt/GSK-3β signals.
authors: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, Shandong 250014, PR China.
authors: Lei
authors: L
authors: Wu
authors: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, Shandong 250014, PR China.
authors: Hua
authors: H
authors: Feng
authors: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, Shandong 250014, PR China.
authors: Jinhua
authors: J
authors: Hu
authors: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, Shandong 250014, PR China.
authors: Xiangguo
authors: X
authors: Tian
authors: Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, Shandong 250014, PR China. Electronic address: chunqingzhangsd@163.com.
authors: Chunqing
authors: C
authors: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D055550:Protein Stability; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D015854:Up-Regulation; D014635:Valproic Acid / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; C498143:RELA protein, human; D000071250:Snail Family Transcription Factors; D051996:Transcription Factor RelA; D014635:Valproic Acid; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: EMT; HCC; NF-κB; Snail; VPA