Propofol exerts anti-hepatocellular carcinoma by microvesicle-mediated transfer of miR-142-3p from macrophage to cancer cells.

OBJECTIVE

We previously confirmed that propofol directly inhibited the viability, proliferation, and invasiveness of hepatocellular carcinoma cells in vitro. In this study, we investigated the mechanism underlying the anti-HCC effects of propofol.

METHODS

In vivo antitumor activity was investigated in tumor-bearing mice following an intraperitoneal injection of propofol, with or without clodrolip. The co-culture system was used to verify that miR-142-3p was transported from macrophages to HCC cells. A miR-142-3p inhibitor was used to down-regulate the expression of miR-142-3p.

RESULTS

Propofol drastically inhibited tumor growth in tomor-bearing mice through macrophage activation, and stimulated tumor-associated macrophages (TAMs) to secrete microvesicles (MVs), which delivered miR-142-3p to HCC cells, resulting in the inhibition of HCC cell invasion. In addition, MVs collected from the plasma of the tumor-bearing mice injected with propofol suppressed tumor growth. More importantly, down-regulation of the expression miR-142-3p reversed the effect of propofol on HCC cell migration.

CONCLUSIONS

This study reveals a novel role for propofol in the inhibition of HCC through MV-mediated transfer of miR-142-3p from macrophages to cancer cells in vivo.