Okadaic acid promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells by inhibiting protein phosphatase 2A.

ABSTRACT

As a specific inhibitor of serine/threonine protein phosphatases, okadaic acid (OA) has been found to be a tumor promoter. However, whether OA plays a role in metastasis of hepatocellular carcinoma (HCC) has not been well elucidated. In this study, Hep3B and HepG2 cells were treated with different doses of OA and the cell viability was determined by CCK8 test. As a result, Hep3B and HepG2 cells showed no obvious cytotoxicity after OA treatment below 20 or 25 nM for 12 or 24 hours. However, wound healing, invasion, and migration abilities of HCC cells were significantly enhanced in the OA-treated groups than those of the control group (P < .05), measured by cell scratching and BD transwell assays. Moreover, we found that the expression of epithelial-mesenchymal transition (EMT)-related key factors was changed upon OA treatment in a dose-dependent manner. In addition, the activity of protein phosphatase 2A (PP2A) in OA-treated cells was also decreased significantly compared with the control cells (P < .05). Interfering of PP2A subunit A or C caused a similar expression change of EMT-related key factors as the OA treatment in HCC cells. Our results suggest that OA promotes the EMT process of HCC cells by inhibiting the activity of PP2A.