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Propofol inhibits the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression |
Jian Zhang, Dan Zhang, Guo-Qing Wu, Zhi-Ying Feng and Sheng-Mei Zhu |
Hangzhou, China
Author Affiliations: Department of Anesthesiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China (Zhang J, Feng ZY and Zhu SM); Department of Gynaecology and Obstetrics, Hangzhou Cancer Hospital, Hangzhou 310002, China (Zhang D); and Department of Oncology, Zhejiang Provincial People’s Hospital, Hangzhou 310014, China (Wu GQ)
Corresponding Author: Sheng-Mei Zhu, PhD, Department of Anesthesiology, First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China (Tel: 86-571-87236169; Email: smzhu20088@yahoo.com.cn) |
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Abstract BACKGROUND: Propofol is one of the extensively and commonly used intravenous anesthetics and has the ability to influence the proliferation, motility, and invasiveness of many cancer cells. In this study, the effects of propofol on hepatocellular carcinoma cells invasion ability were examined.
METHODS: We assessed the invasion ability of HepG2 cells in vitro by determining enzyme activity and protein expression of MMP-9 using gelatin zymography assay and Western blot. The real-time PCR was used to evaluate the effect of propofol on microRNA-199a (miR-199a) expression, and miR-199a-2 precursor to evaluate whether over-expression of miR-199a can affect MMP-9 expression. Finally, the effect of miR-199a on propofol-induced anti-tumor activity using anti-miR-199a was assessed.
RESULTS: Propofol significantly elevated the expression of miR-199a and inhibited the invasiveness of HepG2 cells. Propofol also efficiently decreased enzyme activity and protein expression of MMP-9. Moreover, the over-expression of miR-199a decreased MMP-9 protein level. Interestingly, the neutralization of miR-199a by anti-miR-199a antibody reversed the effect of propofol on alleviation of tumor invasiveness and inhibition of MMP-9 activity in HepG2 cells.
CONCLUSION: Propofol decreases hepatocellular carcinoma cell invasiveness, which is partly due to the down-regulation of MMP-9 expression by miR-199a.
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