[Rosiglitazone inhibits human HepG2 cell proliferation via PI3K/PTEN/Akt signaling pathway]

Meng Zhang1, Li Peng, Zhibin Qiao

  • 1Department of Hepatobiliary Surgery, Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang 050011, China.

Abstract

Insights

Rosiglitazone (ROZ) inhibits hepatocellular carcinoma HepG2 cell proliferation and blocks the cell cycle. These effects are linked to the PI3K/PTEN/Akt pathway, impacting Skp2 and P27(kip1) protein expression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Hepatocellular carcinoma (HCC) is a significant global health concern.
  • Understanding the molecular mechanisms underlying HCC proliferation is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the effects of rosiglitazone (ROZ) on HepG2 cell proliferation and cell cycle.
  • To explore the underlying molecular mechanisms involving key proteins and signaling pathways.

Main Methods:

  • HepG2 cells were treated with varying concentrations of ROZ.
  • Cell proliferation was assessed using MTT assay.
  • Cell cycle distribution was analyzed by flow cytometry.
  • Protein and mRNA expression levels of PTEN, pAkt, Skp2, and P27(kip1) were measured using Western blotting and RT-PCR.

Main Results:

  • ROZ significantly inhibited HepG2 cell proliferation in a dose- and time-dependent manner.
  • ROZ treatment led to an increased proportion of cells in the G0/G1 phase and a decrease in the S phase.
  • ROZ reduced pAkt and Skp2 expression while increasing PTEN and P27(kip1) expression at the protein level.
  • ROZ increased PTEN mRNA and decreased Skp2 mRNA levels, with no significant effect on P27(kip1) mRNA.

Conclusions:

  • ROZ effectively inhibits HepG2 cell proliferation and induces G0/G1 cell cycle arrest.
  • The observed effects are likely mediated through the PI3K/PTEN/Akt signaling pathway.
  • ROZ modulates the expression of Skp2 and P27(kip1), contributing to its anti-cancer effects in HCC.

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