Propofol inhibits the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression.

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.

• Authors: Jian Zhang, Dan Zhang, Guo-Qing Wu, Zhi-Ying Feng, Sheng-Mei Zhu
• Journal: Hepatobiliary & pancreatic diseases international : HBPD INT (Hepatobiliary Pancreat Dis Int) Vol. 12 Issue 3 Pg. 305-9 (Jun 2013) ISSN: 1499-3872 [Print] Singapore
• PMID: 23742776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Intravenous
• MicroRNAs
• mirn199 microRNA, human
• MMP9 protein, human
• Matrix Metalloproteinase 9
• Propofol

Topics

• Anesthetics, Intravenous (pharmacology)
• Carcinoma, Hepatocellular (enzymology, genetics, pathology)
• Cell Adhesion (drug effects)
• Cell Movement (drug effects)
• Dose-Response Relationship, Drug
• Down-Regulation
• Gene Expression Regulation, Enzymologic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Hep G2 Cells
• Humans
• Liver Neoplasms (enzymology, genetics, pathology)
• Matrix Metalloproteinase 9 (metabolism)
• MicroRNAs (metabolism)
• Neoplasm Invasiveness
• Propofol (pharmacology)
• Transfection
• Up-Regulation