Pitavastatin suppressed liver cancer cells in vitro and in vivo

He-Yi You1, Wei-Jian Zhang1, Xue-Meng Xie1

  • 1Department of Telescopic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.

Oncotargets and Therapy
|September 14, 2016
PubMed

Insights

Pitavastatin, a cholesterol drug, shows promise for liver cancer therapy. It effectively inhibits liver cancer cell growth, induces cell cycle arrest, and promotes apoptosis, while reducing tumor growth in mice.

Area of Science:

  • Hepatology
  • Oncology
  • Pharmacology

Background:

  • Pitavastatin is a statin used for lowering blood cholesterol.
  • Previous studies indicated pitavastatin possesses antiglioma stem cell properties.
  • The therapeutic potential of pitavastatin in liver cancer remains unexplored.

Purpose of the Study:

  • To investigate the efficacy of pitavastatin as a potential treatment for liver cancer.
  • To evaluate the cytotoxic effects of pitavastatin on liver cancer cells in vitro and in vivo.
  • To elucidate the mechanisms underlying pitavastatin's anti-liver cancer activity.

Main Methods:

  • Cytotoxicity was assessed using cell viability and colony formation assays on Huh-7 and SMMC7721 liver cancer cell lines.
  • Cell cycle progression was analyzed by flow cytometry following pitavastatin treatment.
  • Apoptosis-related protein expression, including caspase cleavage, was examined, and the effect of a caspase inhibitor (Z-VAD-FMK) was evaluated.
  • In vivo efficacy was tested by assessing tumor growth inhibition and survival rates in tumor-bearing mice.

Main Results:

  • Pitavastatin significantly inhibited the proliferation and colony formation of liver cancer cells.
  • Treatment with pitavastatin led to G1 phase cell cycle arrest and an increased proportion of sub-G1 cells, indicative of apoptosis.
  • Pitavastatin induced the cleavage of caspase-9 and caspase-3, and this apoptotic effect was reversed by the caspase inhibitor Z-VAD-FMK.
  • In vivo studies demonstrated that pitavastatin reduced tumor growth and improved the survival of mice with liver tumors.

Conclusions:

  • Pitavastatin exhibits significant anti-liver cancer effects by inducing apoptosis and inhibiting tumor growth.
  • The drug's mechanism involves caspase activation and cell cycle arrest.
  • Pitavastatin represents a potential repurposed drug for liver cancer therapy.