PPARgamma activator rosiglitazone inhibits cell migration via upregulation of PTEN in human hepatocarcinoma cell line BEL-7404.
PPARgamma agonists were reported to be implicated in many biological functions in certain kinds of cells, however, little is known about the effects of PPARgamma on hepatocarcinoma cell. We explored the effects of rosiglitazone, a PPARgamma activator, on human hepatocarcinoma cell line BEL-7404 and its mechanism. After BEL-7404 was exposed to rosiglitazone, its migration was significantly inhibited, which associated with downregulation of the phosphorylation of Akt and FAK, while no significant change was detected in the phosphorylation of ERK after rosiglitazone treatment. It is now known that phosphorylated FAK is a substrate of PTEN and Akt phosphorylation can be regulated by PTEN via the PIP(3) level. We found rosiglitazone upregulated PTEN expression in a dose- and time-dependent manner, which was mediated by PPARgamma. Furthermore, PTEN overexpression resulted in inhibition of cell migration and PTEN knock-down blocked the effect of rosiglitazone on cell migration. It suggested that PTEN was required for rosiglitazone-induced inhibition of BEL-7404 cells migration. In conclusion, our results demonstrated that PTEN played a critical role in rosiglitazone inhibiting cell migration in BEL-7404.
Zhang
Wen
W
Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.
Wu
Nan
N
Li
Zengxia
Z
Wang
Liying
L
Jin
Jiawei
J
Zha
Xi-Liang
XL
D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008156:Luciferases / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008156:Luciferases; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human