Pitavastatin suppressed liver cancer cells in vitro and in vivo

Abstract

He-Yi You, Wei-Jian Zhang, Xue-Meng Xie, Zhi-Hai Zheng, Heng-Liang Zhu, Fei-Zhao Jiang Department 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. Keywords: liver cancer, apoptosis, chemosensitive, blood cholesterol lowering drug

Keywords

• Pitavastatin
• liver cancer
• apoptosis
• chemo-sensitive
• blood cholesterol lowering drug