[Rosiglitazone inhibits human HepG2 cell proliferation via PI3K/PTEN/Akt signaling pathway].
OBJECTIVE
To investigate the effects of rosiglitazone (ROZ) on proliferation and cell cycle of human hepatocellular carcinoma cell line HepG2 and explore the underlying mechanisms by detecting the related proteins.


METHODS
After treated with ROZ of different concentrations, HepG2 cells were tested for the changes in the cell proliferation by MTT assay and in the cell cycle by flow cytometry. Western blotting and RT-PCR were performed to measure the expressions of PTEN, pAkt, S phase kinase associated protein 2 (Skp2) and P27(kip1); at protein and mRNA levels, respectively. RESULTS ROZ significantly inhibited HepG2 cell proliferation in a concentration-dependent and time-dependent manner (P<0.05). The proportion of HepG2 cells in G0/G1 phase increased, and that in S phase decreased significantly (P<0.05). ROZ reduced the expressions of pAkt and Skp2, and raised the expressions of PTEN and P27(kip1); in HepG2 cells (P<0.05). RT-PCR revealed that ROZ increased the expressions of PTEN mRNA, decreased the expressions of Skp2 mRNA, and had no effect on P27(kip1); mRNA.


CONCLUSIONS
Our study demonstrated that ROZ could inhibit HepG2 cell proliferation and block G0/G1 phase, the mechanisms may be related to the regulation on the expressions of Skp2 and P27(kip1); through the PI3K/PTEN/Akt signaling pathway.
Department of Hepatobiliary Surgery, Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang 050011, China.
Meng
M
Zhang
Li
L
Peng
Zhibin
Z
Qiao
Hongtao
H
He
Ye
Y
Zhou
Zhuo
Z
Xu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000077154:Rosiglitazone; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D045162:Thiazolidinediones / Q000494:pharmacology*
D000970:Antineoplastic Agents; D044786:S-Phase Kinase-Associated Proteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase