Targeting colon cancer stem cells with novel blood cholesterol drug pitavastatin

Z.-Y. Zhang, S.-H. Zheng, W.-G. Yang, C. Yang, W.-T. Yuan

Department of Colorectal Anal Surgery, Department of General Surgery, Department of Emergency Surgery; The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan, China. zhiyongzhang_123@163.com

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• Oncology

OBJECTIVE: Previous studies have demonstrated the importance of stem cells in human cancer, including colon cancer. Pitavastatin is approved for the treatment of hyperlipidemia and has also been shown to inhibit stem cell proliferation in preliminary in vitro studies. This study was done to investigate the effects of pitavastatin on human colon carcinoma stem cells (coCSCs) in vitro and in mouse tumor xenografts in vivo.

MATERIALS AND METHODS: Human colon adenocarcinoma cell lines, SW480 and SW620, were cultured to the spheroid formation. The effects of pitavastatin on colon cancer stem cells were studied using the colorimetric MTT cell proliferation assay; quantitative polymerase chain reaction was used to determine the expression of cell cycle genes, OCT4, SOX2, and NANOG; Western blots were performed to measure MDR1. Mice were injected subcutaneously with SW480 cells; the growth of these tumor xenografts was studied using volumetric analysis following pitavastatin treatment.

RESULTS: Specific cell culture medium provided conditions that resulted in the expression of colon cancer stem cell markers when compared with normal cultured cells. Colon cancer stem cells were inhibited by pitavastatin treatment. Pitavastatin reduced the expression of stem cell markers of colon cancer stem cells and induced the cell apoptosis. Pitavastatin inhibited the growth of mouse tumor xenografts.

CONCLUSIONS: The findings of this preliminary study have demonstrated a potential role for pitavastatin in the inhibition of stem cell proliferation in colon carcinoma. Further studies are recommended to determine the mechanism of these effects on colon carcinoma cells in vitro and in vivo.

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