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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.
Abstract:
Pitavastatin classically functions as a blood cholesterol-lowering drug. Previously, it was discovered with antiglioma stem cell properties through drug screening. However, whether it can be used for liver cancer cell therapy has never been reported. In this study, the cell viability and colony formation assay were utilized to analyze the cytotoxicity of pitavastatin on liver cancer cells. The cell cycle alteration was checked after pitavastatin treatment. Apoptosis-related protein expression and the effect of caspase inhibitor were also checked. The in vivo inhibitory effect of pitavastatin on the growth of liver tumor was also tested. It was found that pitavastatin inhibited growth and colony formation of liver cancer Huh-7 cells and SMMC7721 cells. It induced arrest of liver cancer cells at the G1 phase. Increased proportion of sub-G1 cells was observed after pitavastatin treatment. Pitavastatin promoted caspase-9 cleavage and caspase-3 cleavage in liver cancer cells. Caspase inhibitor Z-VAD-FMK reversed the cleavage of cytotoxic effect of pitavastatin. Moreover, pitavastatin decreased the tumor growth and improved the survival of tumor-bearing mice. This study suggested the antiliver cancer effect of the old drug pitavastatin. It may be developed as a drug for liver cancer therapy.
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.
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